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Precedia/Small molecules/Avmapki Fakzynja Co-pack/Skipped studies

Avmapki Fakzynja Co-pack: genotox, carcinogenicity and repro: done or skipped?

avutometinib and defactinib · RAF/MEK clamp; FAK
Check my plan vs. these
Genotoxicity
Defactinib: Ames and chromosome aberration negative; positive in vitro and in vivo rat micronucleus (aneugenic)
“Defactinib was not mutagenic in the bacterial reverse mutagenesis (Ames) assay and was not clastogenic in an in vitro Chinese hamster lung cell chromosome aberration assay. Defactinib was positive in the in vitro micronucleus assay through an aneugenic mechanism and in the in vivo rat bone marrow micronucleus assay.”
✓ VerifiedFDA multi-discipline review, p. 38Source ↗
Carcinogenicity
Not conducted (advanced cancer indication)
“The Applicant did not conduct carcinogenicity studies with avutometinib; it is also not warranted to support the marketing application of AVMAPKI FAKZYNJA CO-PACK for the proposed indication.”
✓ VerifiedFDA multi-discipline review, p. 36Source ↗
Instead of carcinogenicity
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Instead of genotoxicity
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
DRG histopathology
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Reproductive & developmental
Not conducted for either drug; embryo-fetal toxicity assessed by weight of evidence
“The Applicant did not conduct any reproductive toxicology studies with avutometinib and defactinib.”
✓ VerifiedFDA multi-discipline review, p. 39Source ↗
Safety pharmacology
Avutometinib: weak hERG inhibitor, little or no QT risk
“In safety pharmacology studies, avutometinib was found to be a weak inhibitor of the hERG channel current. As such, the data suggests that avutometinib may pose little or no risk for QT interval effects.”
✓ VerifiedFDA multi-discipline review, p. 35Source ↗
Genotox: Ames
Defactinib: negative
“Defactinib was not mutagenic in the bacterial reverse mutagenesis (Ames) assay and was not clastogenic in an in vitro Chinese hamster lung cell chromosome aberration assay.”
✓ VerifiedFDA multi-discipline review, p. 38Source ↗
Genotox: in vitro mammalian
Defactinib: chromosome aberration (CHL) negative; in vitro micronucleus positive (aneugenic)
“Defactinib was not mutagenic in the bacterial reverse mutagenesis (Ames) assay and was not clastogenic in an in vitro Chinese hamster lung cell chromosome aberration assay. Defactinib was positive in the in vitro micronucleus assay through an aneugenic mechanism and in the in vivo rat bone marrow micronucleus assay.”
✓ VerifiedFDA multi-discipline review, p. 38Source ↗
Genotox: in vivo
Defactinib: rat bone marrow micronucleus positive
“Defactinib was positive in the in vitro micronucleus assay through an aneugenic mechanism and in the in vivo rat bone marrow micronucleus assay.”
✓ VerifiedFDA multi-discipline review, p. 38Source ↗
Carcinogenicity model
Not conducted (not warranted for the proposed indication)
“The Applicant did not conduct carcinogenicity studies with avutometinib; it is also not warranted to support the marketing application of AVMAPKI FAKZYNJA CO-PACK for the proposed indication.”
✓ VerifiedFDA multi-discipline review, p. 36Source ↗
Carcinogenicity timing
Not required for the advanced cancer indication
“The Applicant did not conduct carcinogenicity studies with avutometinib; it is also not warranted to support the marketing application of AVMAPKI FAKZYNJA CO-PACK for the proposed indication.”
✓ VerifiedFDA multi-discipline review, p. 36Source ↗
hERG / QT
Avutometinib: weak hERG inhibitor; little or no QT risk
“In safety pharmacology studies, avutometinib was found to be a weak inhibitor of the hERG channel current. As such, the data suggests that avutometinib may pose little or no risk for QT interval effects.”
✓ VerifiedFDA multi-discipline review, p. 35Source ↗

Same question, other small molecules

Accrufer

ferric maltol · Iron replacement
Ferric maltol positive in Ames; maltol positive in Ames and in vivo mouse micronucleus assay

Adquey

difamilast · PDE4 (topical)
Negative in Ames, mouse lymphoma and rat micronucleus assays

Agamree

vamorolone · Glucocorticoid receptor (dissociative)
Negative in Ames, mouse lymphoma gene mutation and mouse micronucleus assays

Alyftrek

vanzacaftor, tezacaftor and deutivacaftor · CFTR
Vanzacaftor negative in Ames, in vitro TK6 micronucleus and in vivo rat micronucleus assays

Anzupgo

delgocitinib · Pan-JAK (topical)
Ames negative; polyploidy in human lymphocytes in vitro; negative in vivo rat bone marrow chromosome aberration assay

Aqneursa

levacetylleucine · Neuronal metabolism (proposed)
Negative in Ames, in vitro human lymphocyte chromosome aberration and in vivo rat bone marrow assays

Artesunate

artesunate · Plasmodium (antimalarial)
Negative in Ames, CHO chromosome aberration and in vivo micronucleus assays

Attruby

acoramidis · Transthyretin (stabiliser)
Negative in Ames, rat micronucleus and alkaline comet assays

Augtyro

repotrectinib · ROS1/TRK
Ames negative; genotoxic via aneugenic mechanism in vitro (TK6 cells) and in vivo rat bone marrow micronucleus assay

Ayvakit

avapritinib · KIT/PDGFRA
Ames negative; positive in vitro chromosome aberration; negative rat bone marrow micronucleus; overall non-genotoxic

Azstarys

serdexmethylphenidate and dexmethylphenidate · Dopamine/norepinephrine reuptake
Negative in Ames, in vitro human lymphocyte micronucleus, in vivo rat bone marrow micronucleus and rat comet assays

Balversa

erdafitinib · FGFR1-4
Negative in Ames, in vitro micronucleus and in vivo rat bone marrow micronucleus assays

Barhemsys

amisulpride · Dopamine D2/D3 receptor
Negative in Ames, in vitro human lymphocyte chromosome aberration and rat micronucleus assays

Baxfendy

baxdrostat · Aldosterone synthase (CYP11B2)
Not genotoxic in a battery of in vitro and in vivo assays

Beqalzi

sonrotoclax · BCL-2
Negative in Ames, in vitro chromosomal aberration and mouse bone marrow micronucleus assays

Blujepa

gepotidacin · Bacterial topoisomerases (gyrase/topo IV)
Positive in vitro (human lymphocyte micronucleus, mouse lymphoma); negative in vivo rat micronucleus and comet assays

Brenzavvy

bexagliflozin · SGLT2
Negative in Ames, in vitro CHO chromosomal aberration, in vivo rat micronucleus and rat unscheduled DNA synthesis assays

Brexafemme

ibrexafungerp · Fungal glucan synthase
Negative in Ames, in vitro chromosome aberration and rat bone marrow micronucleus assays

Brinsupri

brensocatib · DPP1 (cathepsin C)
Negative in Ames, in vitro mouse lymphoma TK and in vivo rat micronucleus assays

Brukinsa

zanubrutinib · BTK
Negative in Ames, in vitro chromosomal aberration and rat bone marrow micronucleus assays

Byfavo

remimazolam · GABA-A receptor (benzodiazepine site)
Negative in Ames, mouse lymphoma and in vivo rat micronucleus assays

Bylvay

odevixibat · IBAT
Negative in Ames, in vitro mouse lymphoma and in vivo rat micronucleus assays

Cabenuva

cabotegravir and rilpivirine · HIV-1 integrase; NNRTI
Negative in Ames and in vivo rat micronucleus assays

Camzyos

mavacamten · Cardiac myosin
Negative in Ames, human lymphocyte clastogenicity and rat micronucleus assays

Caplyta

lumateperone · 5-HT2A / D2 receptor
Ames and mouse lymphoma positive only with metabolic activation; negative rat micronucleus and Comet

Cardamyst

etripamil · L-type calcium channel
Negative in Ames, in vitro chromosome aberration and in vivo rat micronucleus (IV) assays

Cibinqo

abrocitinib · JAK1
Ames negative; aneugenic in in vitro micronucleus assay; negative in vivo rat micronucleus

Cobenfy

xanomeline and trospium · Muscarinic M1/M4 agonist; peripheral antagonist
Xanomeline negative in Ames, mouse lymphoma, rat hepatocyte UDS, CHO chromosome aberration and mouse micronucleus assays

Cosela

trilaciclib · CDK4/6
Ames negative; negative for clastogenicity in human fibroblasts; increased micronuclei in human lymphocytes in vitro

Crenessity

crinecerfont · CRF1 receptor
Negative in Ames, in vitro chromosomal aberration and in vivo rat bone marrow micronucleus assays

Cypsedo

cipepofol · GABA-A receptor
Negative in Ames, in vitro chromosomal aberration and mouse bone marrow micronucleus assays

Daybue

trofinetide · IGF-1 tripeptide analogue
Negative in Ames, in vitro CHO chromosomal aberration and in vivo mouse micronucleus assays

Dayvigo

lemborexant · Orexin OX1/OX2 receptors
Negative in Ames, mouse lymphoma TK and in vivo rat micronucleus assays

Defencath

taurolidine and heparin · Antimicrobial catheter lock
Taurolidine positive in vitro (mouse lymphoma and Ames) regardless of metabolic activation; negative in vivo

Dojolvi

triheptanoin · Anaplerotic energy substrate
Negative in Ames, in vitro chromosome aberration (human lymphocytes) and in vivo rat micronucleus assays

Duvyzat

givinostat · Histone deacetylase (class I/II)
Positive in Ames; negative in mouse lymphoma, human lymphocyte chromosome aberration and in vivo Big Blue rat (Pig-a) assays

Egaten

triclabendazole · Fasciola (tubulin)
Negative in a 6-assay battery including Ames, chromosome aberration and micronucleus assays

Ekterly

sebetralstat · Plasma kallikrein
Negative in Ames, mouse lymphoma and in vivo rat micronucleus assays

Ensacove

ensartinib · ALK
Negative in Ames, in vitro human lymphocyte chromosome aberration and in vivo rat micronucleus assays

Evrysdi

risdiplam · SMN2 splicing
Ames negative; clastogenic (micronucleus) in vitro in mouse lymphoma cells and in vivo in rat bone marrow

Exblifep

cefepime and enmetazobactam · PBPs; beta-lactamase (enmetazobactam)
Enmetazobactam negative in Ames, CHO chromosomal aberration and mouse bone marrow micronucleus assays

Exkivity

mobocertinib · EGFR exon 20 insertion
Negative in Ames, in vitro chromosome aberration (human lymphocytes) and in vivo rat bone marrow micronucleus assays

Exxua

gepirone · 5-HT1A receptor
Negative in Ames, CHO/HGPRT, hepatocyte DNA repair, rat micronucleus and 5-hour CHO chromosome aberration assays

Fabhalta

iptacopan · Complement factor B
Not genotoxic or mutagenic in a battery of in vitro and in vivo assays

Fetroja

cefiderocol · Penicillin-binding proteins
Ames negative; chromosomal aberrations in vitro; negative in vivo rat micronucleus and liver comet assays

Fexinidazole

fexinidazole · Trypanosoma brucei
Positive in Ames; negative in in vitro human lymphocyte micronucleus and in vivo mouse bone marrow micronucleus assays

Filspari

sparsentan · Endothelin A / angiotensin II receptors
Negative in Ames, in vitro chromosomal aberration and in vivo rat micronucleus assays

Fotivda

tivozanib · VEGFR1-3
Negative in Ames, in vitro CHO cytogenetic and in vivo mouse bone marrow micronucleus assays

Foundayo

orforglipron · GLP-1 receptor (non-peptide)
Negative in Ames, in vitro micronucleus (human lymphoblastoid cells) and in vivo rat bone marrow micronucleus assays

Fruzaqla

fruquintinib · VEGFR1-3
Negative in Ames, in vitro CHO chromosome aberration and in vivo rat micronucleus assays

Gavreto

pralsetinib · RET
Negative in Ames, in vitro TK6 micronucleus and rat bone marrow micronucleus assays

Gemtesa

vibegron · β3-adrenergic receptor
Negative in Ames, human lymphocyte chromosome aberration and rat bone marrow micronucleus assays

Gomekli

mirdametinib · MEK1/2
Negative Ames; not clastogenic in vitro or in rat chromosome aberration assay; positive rat micronucleus

Grafapex

treosulfan · DNA alkylation
Mutagenic in Ames test and clastogenic in in vitro human lymphocyte micronucleus assay

Hernexeos

zongertinib · HER2 (mutant)
Negative in Ames and rat in vivo micronucleus/comet (liver, duodenum) assays

Hyrnuo

sevabertinib · HER2 (mutant)
Negative in Ames, in vitro micronucleus and in vivo rat micronucleus assays

Ibsrela

tenapanor · NHE3
Negative in Ames, human lymphocyte chromosome aberration and in vivo micronucleus assays

Ibtrozi

taletrectinib · ROS1
Negative in Ames and additional mutagenicity tests and in the rat bone marrow/liver micronucleus assay

Idvynso

doravirine and islatravir · NNRTI; NRTTI
Islatravir: in vitro CHO chromosomal aberrations (mitigated by inosine); negative Ames and in vivo rat micronucleus

Inluriyo

imlunestrant · Estrogen receptor (SERD)
Ames negative; positive in vitro micronucleus; negative in vivo rat comet and bone marrow micronucleus assays

Inpefa

sotagliflozin · SGLT1/SGLT2
Negative in Ames, in vitro CHO chromosomal aberration and in vivo rat bone marrow micronucleus assays

Inqovi

decitabine and cedazuridine · DNMT (decitabine); cytidine deaminase (cedazuridine)
Cedazuridine positive in Ames and in vitro chromosome aberration assays; negative in in vivo micronucleus

Inrebic

fedratinib · JAK2
Negative in Ames, in vitro CHO chromosomal aberration and rat micronucleus assays

Iqirvo

elafibranor · PPARα/δ
Negative in Ames, rat micronucleus and rat comet assays; positive in mouse lymphoma cells

Isturisa

osilodrostat · 11β-hydroxylase (CYP11B1)
Ames and micronucleus negative; structural aberrations in in vitro chromosome aberration assay

Itovebi

inavolisib · PI3Kα (mutant-selective)
Ames negative; clastogenic in vitro (human lymphocyte micronucleus); negative in vivo rat bone marrow micronucleus and liver comet

Jascayd

nerandomilast · PDE4B
Negative in Ames, in vitro chromosome aberration and in vivo micronucleus assays

Jaypirca

pirtobrutinib · BTK (non-covalent)
Ames negative; aneugenic in in vitro human lymphocyte micronucleus assays; negative in in vivo rat bone marrow micronucleus assay

Jesduvroq

daprodustat · HIF prolyl hydroxylase
Negative in Ames, in vitro human lymphocyte chromosomal aberration and in vivo rat bone marrow micronucleus assays

Jideytro

zidesamtinib · ROS1
Positive in in vivo rat micronucleus assays; negative in Ames and in vitro TK6 clastogenicity assay

Joenja

leniolisib · PI3Kδ
Negative in Ames, in vitro chromosomal aberration, in vitro TK6 micronucleus and in vivo rat micronucleus assays

Journavx

suzetrigine · NaV1.8
Negative in Ames, in vitro TK6 micronucleus and in vivo rat bone marrow micronucleus assays

Kerendia

finerenone · Mineralocorticoid receptor
Negative in Ames, in vitro chromosomal aberration and in vivo mouse micronucleus assays

Klisyri

tirbanibulin · Tubulin / Src
Genotoxic: Ames negative; positive in CHO chromosome aberration, mouse lymphoma and rat micronucleus assays

Komzifti

ziftomenib · Menin-KMT2A
Negative in Ames, in vitro micronucleus and in vivo mouse bone marrow micronucleus assays

Koselugo

selumetinib · MEK1/2
Not mutagenic or clastogenic in vitro; positive (aneugenic) mouse micronucleus at >160 mg/kg (~38x human Cmax)

Krazati

adagrasib · KRAS G12C
Negative in Ames, in vitro chromosomal aberration and in vivo rat micronucleus assays

Kygevvi

doxecitine and doxribtimine · Pyrimidine nucleoside replacement (TK2 deficiency)
Negative in Ames and rat micronucleus; positive in vitro chromosome aberration assay in human lymphocytes

Lampit

nifurtimox · Trypanosoma cruzi
Considered genotoxic by weight of evidence; labeled with a genotoxicity Warning

Lazcluze

lazertinib · EGFR (mutant-selective)
Negative in Ames, in vitro chromosome aberration (CHL cells) and rat bone marrow micronucleus assays

Leqselvi

deuruxolitinib · JAK1/JAK2
Negative in Ames, in vitro chromosome aberration and rat bone marrow micronucleus; positive in vitro micronucleus (likely aneugenic)

Lifyorli

relacorilant · Glucocorticoid receptor (antagonist)
Negative in Ames, in vitro human lymphocyte micronucleus and in vivo rat micronucleus assays

Litfulo

ritlecitinib · JAK3/TEC kinases
Aneugenic in in vitro TK6 micronucleus assay; Ames negative

Livdelzi

seladelpar · PPARδ
Negative in Ames, mouse lymphoma and in vivo mouse micronucleus assays

Livmarli

maralixibat · IBAT (ASBT)
Negative in Ames, in vitro CHO chromosome aberration and in vivo rat micronucleus assays

Livtencity

maribavir · CMV UL97 protein kinase
Negative in Ames and in vivo rat micronucleus; mutagenic without metabolic activation in mouse lymphoma assay; overall not genotoxic

Lumakras

sotorasib · KRAS G12C
Negative in Ames and in vivo rat micronucleus and comet assays; some in vitro micronucleus induction

Lupkynis

voclosporin · Calcineurin
Negative in Ames, CHO chromosomal aberration and rat in vivo micronucleus assays

Lybalvi

olanzapine and samidorphan · D2/5-HT2A; opioid receptors (samidorphan)
Samidorphan negative in a standard genotoxicity battery

Lynavoy

linerixibat · IBAT
Negative in Ames, in vitro CHO chromosome aberration and in vivo rat micronucleus assays

Lynkuet

elinzanetant · NK1/NK3 receptors
Negative in Ames, mouse lymphoma and rat bone marrow micronucleus assays

Lytgobi

futibatinib · FGFR1-4 (covalent)
Negative Ames; clastogenic in vitro chromosome aberration assay; negative rat micronucleus and comet assays

Mayzent

siponimod · S1P1/S1P5 receptor
Negative in Ames, mammalian cell assays and mouse and rat micronucleus assays

Miebo

perfluorohexyloctane · Tear film evaporation barrier
Negative in Ames, in vitro human lymphocyte chromosome aberration and in vivo rat bone marrow micronucleus assays

Miplyffa

arimoclomol · Heat-shock response amplifier
Negative in Ames, mouse lymphoma forward mutation and in vivo mouse micronucleus assays

Modeyso

dordaviprone · DRD2 antagonist / ClpP agonist
Negative in Ames, in vitro and in vivo micronucleus assays

Myqorzo

aficamten · Cardiac myosin
Negative in Ames, combined in vivo micronucleus and comet assays

Nereus

tradipitant · NK1 receptor
Negative in Ames, in vitro human lymphocyte chromosomal aberration and mouse micronucleus assays

Nexletol

bempedoic acid · ATP citrate lyase
Ames negative; chromosome aberrations in human lymphocytes only with S9 at cytotoxic concentration

Nextstellis

drospirenone and estetrol · Estrogen / progestin receptors
Estetrol negative in Ames, mouse lymphoma, rat micronucleus and rat Comet assays (weight of evidence)

Nourianz

istradefylline · Adenosine A2A receptor
Negative in Ames (4 assays), CHL chromosome aberration, mouse micronucleus and rat UDS assays

Nubeqa

darolutamide · Androgen receptor
Negative Ames and in vivo rat micronucleus/comet; clastogenic in vitro in human lymphocytes; overall no genotoxic risk

Nulibry

fosdenopterin · cPMP replacement (MoCD type A)
Negative in the standard ICH S2(R1) battery, in vitro and in vivo

Nurtec ODT

rimegepant · CGRP receptor
Negative in Ames, in vitro chromosome aberration and rat bone marrow micronucleus assays

Nuzolvence

zoliflodacin · Bacterial topoisomerase II
Negative in mouse lymphoma and rat micronucleus assays; Ames positive in TA102, consistent with mechanism

Ogsiveo

nirogacestat · Gamma secretase
Negative in Ames, in vitro human chromosome aberration and in vivo rat bone marrow micronucleus assays

Ohtuvayre

ensifentrine · PDE3/PDE4
Negative in Ames, in vivo rat comet (lung and liver) and mouse micronucleus assays

Ojemda

tovorafenib · RAF (type II pan-RAF)
Not genotoxic overall: in vitro chromosomal aberrations only at precipitating concentrations; in vivo micronucleus negative

Ojjaara

momelotinib · JAK1/JAK2/ACVR1
Negative in Ames, human lymphocyte chromosome aberration and in vivo micronucleus assays

Olinvyk

oliceridine · μ-opioid receptor (G-protein biased)
Negative in Ames, in vitro chromosome aberration and rat micronucleus assays

Omlonti

omidenepag isopropyl · EP2 receptor
Negative in Ames and in vivo micronucleus; positive (mutagenic and clastogenic) in in vitro mouse lymphoma assay

Ongentys

opicapone · COMT
Negative in Ames, in vitro chromosome aberration (human lymphocytes) and mouse micronucleus assays

Orgovyx

relugolix · GnRH receptor
Negative in Ames, in vitro chromosome aberration and rat bone marrow micronucleus assays

Orladeyo

berotralstat · Plasma kallikrein
Negative in Ames, in vitro human lymphocyte chromosomal aberration and rat micronucleus assays

Orlynvah

sulopenem etzadroxil and probenecid · Penicillin-binding proteins
Ames negative; chromosome aberrations positive in vitro; negative in vivo rat bone marrow micronucleus

Orserdu

elacestrant · Estrogen receptor (SERD)
Negative in Ames, in vitro chromosome aberration and in vivo rat bone marrow micronucleus assays

Orzeyful

oveporexton · Orexin OX2 receptor agonist
Negative in Ames and in vivo micronucleus; positive in vitro micronucleus (24-hour); overall non-genotoxic

Oxbryta

voxelotor · HbS polymerisation
Negative in Ames, rat Comet and rat micronucleus assays

Palsonify

paltusotine · Somatostatin receptor 2
Negative in Ames, in vitro CHO micronucleus and in vivo rat bone marrow micronucleus assays

Paxlovid

nirmatrelvir and ritonavir · SARS-CoV-2 Mpro (3CL protease)
Nirmatrelvir negative in Ames, in vitro TK6 micronucleus and in vivo rat micronucleus assays

Pemazyre

pemigatinib · FGFR1-3
Negative in Ames, in vitro chromosome aberration (human lymphocytes) and rat bone marrow micronucleus assays

Piqray

alpelisib · PI3Kα
Negative in Ames, in vitro micronucleus and chromosome aberration, and in vivo rat micronucleus assays

Pizensy

lactitol · Osmotic laxative
Not conducted by the applicant; published studies negative in Ames, chromosome aberration and in vivo mouse micronucleus tests

Ponvory

ponesimod · S1P1 receptor
Negative in Ames, in vitro chromosomal aberration and rat micronucleus assays

Pretomanid

pretomanid · Mycobacterial cell wall / respiration
Negative in conventional genotoxicity battery; circulating metabolite M50 mutagenic in Ames

Pyrukynd

mitapivat · Pyruvate kinase (activator)
Negative in Ames, in vitro human lymphocyte micronucleus and in vivo rat bone marrow micronucleus assays

Qelbree

viloxazine · Norepinephrine reuptake
Negative in Ames, in vitro chromosomal aberration and rat bone marrow micronucleus assays

Qinlock

ripretinib · KIT/PDGFRA
Negative in Ames, in vitro chromosomal aberration, and in vivo rat micronucleus and comet assays

Qulipta

atogepant · CGRP receptor
Negative in Ames, in vitro chromosomal aberration and in vivo rat bone marrow micronucleus assays

Quviviq

daridorexant · Orexin OX1/OX2 receptors
Negative in Ames, in vitro chromosome aberration (human lymphocytes) and in vivo rat micronucleus assays

Rapiblyk

landiolol · β1-adrenergic receptor
Negative in Ames, in vitro mouse lymphoma TK and in vivo rat micronucleus assays

Rasonque

daraxonrasib · RAS(ON) multi-selective
Negative in Ames, in vitro human lymphocyte micronucleus and in vivo mouse micronucleus assays

Recarbrio

imipenem, cilastatin and relebactam · Beta-lactamase (relebactam)
Relebactam negative in Ames, chromosomal aberration and rat bone marrow micronucleus assays

Relyvrio

sodium phenylbutyrate and taurursodiol · ER stress / mitochondrial (proposed)
Negative in Ames, in vitro chromosome aberration (human lymphocytes) and in vivo mouse micronucleus assays

Retevmo

selpercatinib · RET
Negative in Ames and in vitro micronucleus; positive in rat in vivo micronucleus at high doses

Revtorpyk

gedatolisib · PI3K/mTOR
Negative in Ames, human lymphocyte chromosomal aberration and rat bone marrow micronucleus assays

Revuforj

revumenib · Menin-KMT2A
Negative in Ames, in vitro micronucleus and in vivo rat micronucleus assays

Reyvow

lasmiditan · 5-HT1F receptor
Negative in Ames, in vitro chromosome aberration and mouse bone marrow micronucleus assays

Rezdiffra

resmetirom · Thyroid hormone receptor β
Negative in Ames, in vitro chromosome aberration, in vitro micronucleus and in vivo rat micronucleus assays

Rezlidhia

olutasidenib · IDH1 (mutant)
Negative in Ames, in vitro human lymphocyte micronucleus and in vivo rat bone marrow micronucleus assays

Rezurock

belumosudil · ROCK2
Negative in Ames, in vitro chromosomal aberration and rat bone marrow micronucleus assays

Rezzayo

rezafungin · Fungal glucan synthase
Negative in Ames, in vitro mammalian clastogenicity and in vivo rat bone marrow micronucleus assays

Rhapsido

remibrutinib · BTK
Negative in Ames, in vitro human lymphocyte micronucleus and in vivo rat micronucleus assays

Rinvoq

upadacitinib · JAK1
Negative in Ames and in vivo rat micronucleus; in vitro chromosome aberration negative for structural, positive for numerical (polyploidy)

Romvimza

vimseltinib · CSF1R
Negative in vivo rat bone marrow micronucleus and liver DNA strand-break assays; overall negative for genotoxicity

Rozlytrek

entrectinib · TRK/ROS1/ALK
Ames negative; aneugenic in vitro (human lymphocytes); negative in rat micronucleus and comet assays

Rukobia

fostemsavir · HIV-1 gp120 (attachment)
Negative in Ames, human lymphocyte chromosome aberration and rat bone marrow micronucleus assays

Scemblix

asciminib · BCR-ABL1 (STAMP, myristoyl pocket)
Negative in Ames, in vitro human lymphocyte micronucleus and in vivo rat reticulocyte micronucleus assays

Sephience

sepiapterin · Tetrahydrobiopterin precursor
Not genotoxic overall: Ames negative; in vitro chromosome aberration positive without (not with) metabolic activation; rat micronucleus and comet negative

Simtriyo

centanafadine · Triple monoamine reuptake
Negative in Ames, CHO chromosome aberration and rat in vivo micronucleus assays

Skyclarys

omaveloxolone · Nrf2 activator
Negative Ames; positive in vitro chromosomal aberration (human lymphocytes); negative in vivo rat micronucleus and comet assays

Sofdra

sofpironium · Muscarinic receptors (topical)
Negative in Ames, in vitro chromosome aberration and rat micronucleus assays

Sohonos

palovarotene · RARγ
Negative Ames and mouse micronucleus; in vitro chromosomal aberration positive only at cytotoxic concentrations

Sotyktu

deucravacitinib · TYK2
Negative in Ames, in vitro chromosome aberration and in vivo rat micronucleus assays; major metabolites also negative

Sunlenca

lenacapavir · HIV-1 capsid
Negative in Ames, in vitro human lymphocyte chromosome aberration and in vivo rat micronucleus assays

Sunosi

solriamfetol · Dopamine/norepinephrine reuptake
Negative in an adequate battery of genotoxicity assays

Tabrecta

capmatinib · MET
Negative in Ames, in vitro chromosome aberration (human lymphocytes) and rat bone marrow micronucleus assays

Tavneos

avacopan · C5a receptor (C5aR1)
Negative in Ames, mouse lymphoma and in vivo rat bone marrow micronucleus assays

Tazverik

tazemetostat · EZH2
Negative in Ames, in vitro micronucleus (human lymphocytes) and in vivo rat micronucleus assays

Tepmetko

tepotinib · MET
Negative in Ames, in vitro and in vivo micronucleus assays (parent and M506)

Trikafta

elexacaftor, tezacaftor and ivacaftor · CFTR
Elexacaftor negative in bacterial and mammalian in vitro assays and an in vivo chromosomal damage assay

Truqap

capivasertib · AKT1-3
Negative in Ames and mouse lymphoma assays; positive (aneugenic) in rat bone marrow micronucleus; negative liver comet

Truseltiq

infigratinib · FGFR1-3
Negative in Ames, in vitro human lymphocyte chromosome aberration and in vivo rat bone marrow micronucleus assays

Tryptyr

acoltremon · TRPM8 agonist
Negative in Ames, in vitro chromosomal aberration (human lymphocytes) and rat micronucleus assays

Tryvio

aprocitentan · Endothelin A/B receptors
Negative in Ames, in vitro chromosomal aberration and in vivo rat micronucleus assays

Tukysa

tucatinib · HER2
Negative in Ames, in vitro chromosome aberration and mouse bone marrow micronucleus assays

Turalio

pexidartinib · CSF1R
Negative in Ames, in vitro chromosome aberration (human lymphocytes) and rat bone marrow micronucleus assays

Ubrelvy

ubrogepant · CGRP receptor
Negative in Ames, in vitro chromosomal aberration and in vivo rat bone marrow micronucleus assays

Ukoniq

umbralisib · PI3Kδ / CK1ε
Negative in Ames, in vitro TK6 micronucleus and in vivo mouse micronucleus assays

Utebzi

tebipenem pivoxil · Penicillin-binding proteins
Prodrug positive in vitro (mammalian gene mutation, CHO chromosomal aberration); negative in mouse bone marrow micronucleus

Vafseo

vadadustat · HIF prolyl hydroxylase
Ames negative; clastogenic in two in vitro assays; negative in vivo rat comet and chromosome aberration assays; not genotoxic overall

Vanflyta

quizartinib · FLT3
Positive in Ames; negative in mouse lymphoma, human lymphocyte chromosome aberration and rat micronucleus assays

Vanrafia

atrasentan · Endothelin A receptor
Negative in Ames, in vitro chromosomal aberration and in vivo mouse micronucleus assays

Veklury

remdesivir · SARS-CoV-2 RNA polymerase
Negative in Ames, human lymphocyte chromosome aberration and rat micronucleus assays

Velsipity

etrasimod · S1P1/S1P4/S1P5 receptors
Negative in Ames, human lymphocyte chromosomal aberration and rat micronucleus assays

Veozah

fezolinetant · Neurokinin-3 receptor
Negative in Ames, chromosomal aberration and in vivo micronucleus tests

Veppanu

vepdegestrant · Estrogen receptor (PROTAC degrader)
Negative in Ames (parent and ARV-473), in vitro human lymphocyte micronucleus and in vivo rat micronucleus assays

Verquvo

vericiguat · Soluble guanylate cyclase
Negative in Ames, mouse lymphoma and rat and mouse micronucleus assays

Vivjoa

oteseconazole · Fungal CYP51
Negative in Ames, in vitro chromosome aberration and rat micronucleus assays

Vizz

aceclidine · Muscarinic agonist (miotic)
Negative in Ames (Salmonella and E. coli), in vitro chromosome aberration and mouse micronucleus assays

Vonjo

pacritinib · JAK2/FLT3
Negative in Ames, in vitro chromosome aberration (CHO) and in vivo mouse micronucleus assays

Voquezna

vonoprazan · H+/K+-ATPase (potassium-competitive)
Negative in Ames, CHL chromosomal aberration and rat bone marrow micronucleus assays

Voranigo

vorasidenib · IDH1/IDH2
Negative in Ames, in vitro micronucleus, chromosomal aberration and rat bone marrow micronucleus assays (parent and AGI-69460)

Voydeya

danicopan · Complement factor D
Negative in Ames, in vitro human lymphocyte micronucleus and in vivo rat micronucleus assays

Vtama

tapinarof · Aryl hydrocarbon receptor
Negative in Ames, in vitro chromosome aberration, mouse lymphoma and mouse and rat micronucleus assays

Vyndaqel

tafamidis · Transthyretin (stabiliser)
Negative in Ames, in vitro human lymphocyte chromosomal aberration and in vivo rat micronucleus assays

Wakix

pitolisant · Histamine H3 receptor
Negative in Ames, in vitro chromosomal aberration and in vivo mouse micronucleus assays

Wayrilz

rilzabrutinib · BTK (reversible covalent)
Negative in Ames, in vitro human lymphocyte chromosome aberration and rat bone marrow micronucleus assays

Welireg

belzutifan · HIF-2α
Negative in Ames, in vitro human lymphocyte micronucleus and in vivo rat bone marrow micronucleus assays

Winlevi

clascoterone · Androgen receptor (topical)
No clear genotoxic potential; negative Ames and in vitro chromosome aberration assays

Xacduro

sulbactam and durlobactam · PBPs; beta-lactamase (durlobactam)
Durlobactam negative in in vivo rat micronucleus assay up to 2000 mg/kg

Xcopri

cenobamate · Sodium channel / GABA-A
Negative in Ames, mouse lymphoma and rat bone marrow micronucleus assays

Xdemvy

lotilaner · Mite GABA-Cl channel
Negative in Ames, in vitro chromosome aberration (human lymphocytes) and rat micronucleus assays

Xeglyze

abametapir · Lice metalloproteinases
Ames negative (parent and COOH metabolite); chromosome aberrations only at cytotoxic concentrations; rat micronucleus negative

Xenleta

lefamulin · Bacterial ribosome (50S PTC)
Negative in in vivo rat bone marrow micronucleus and in vitro mouse lymphoma assays

Xocova

ensitrelvir · SARS-CoV-2 3CL protease
Negative in Ames, in vitro TK6 micronucleus and in vivo rat micronucleus assays

Xolremdi

mavorixafor · CXCR4
Negative in Ames, in vitro chromosome aberration (human lymphocytes) and rat micronucleus assays

Xpovio

selinexor · XPO1
Negative in Ames, in vitro human lymphocyte cytogenetic and in vivo rat micronucleus assays

Zavzpret

zavegepant · CGRP receptor
Negative in Ames, in vitro CHO chromosomal aberration and in vivo rat micronucleus assays

Zaynich

cefepime and zidebactam · PBPs; beta-lactam enhancer (zidebactam)
Zidebactam negative in mouse lymphoma, human lymphocyte chromosomal aberration and mouse micronucleus assays

Zegfrovy

sunvozertinib · EGFR exon 20 insertion
Negative in Ames, in vitro CHO chromosome aberration and rat bone marrow micronucleus assays

Zenbexus

iberdomide · Cereblon (CELMoD)
In vitro chromosomal aberrations at ≥550 µg/mL; Ames and in vivo assays negative; not considered genotoxic

Zeposia

ozanimod · S1P1/S1P5 receptor
Ozanimod negative (Ames, mouse lymphoma, rat micronucleus); metabolite CC1084037 positive in vitro chromosome aberration, negative in vivo

Zepzelca

lurbinectedin · DNA minor groove (transcription)
Ames negative; positive in mouse lymphoma TK assay; genotoxic

Zevtera

ceftobiprole medocaril · Penicillin-binding proteins
Negative in vivo (micronucleus and rat liver UDS), reducing concern over clastogenic signals in vitro

Zokinvy

lonafarnib · Farnesyltransferase
Negative in Ames, in vitro human lymphocyte chromosomal aberration and mouse micronucleus assays

Ztalmy

ganaxolone · GABA-A receptor (positive modulator)
Negative in Ames, mouse lymphoma and rat micronucleus assays; human metabolite M2 clastogenic in vitro

Zulresso

brexanolone · GABA-A receptor (positive modulator)
Negative in Ames, in vitro human lymphocyte micronucleus and in vivo rat bone marrow micronucleus assays

Zurzuvae

zuranolone · GABA-A receptor (positive modulator)
Negative in Ames, in vitro chromosomal aberration and rat bone marrow micronucleus assays

Zycubo

copper histidinate · Copper replacement (Menkes disease)
Negative in Ames, in vitro TK6 micronucleus and rat bone marrow micronucleus assays

Summary across all 211 small molecules →