Accrufer
ferric maltol · Iron replacementFerric maltol positive in Ames; maltol positive in Ames and in vivo mouse micronucleus assay
Voranigo: genotox, carcinogenicity and repro: done or skipped?
vorasidenib · IDH1/IDH2
Genotoxicity
Negative in Ames, in vitro micronucleus, chromosomal aberration and rat bone marrow micronucleus assays (parent and AGI-69460)
“Vorasidenib and its major circulating metabolite, AGI-69460, were negative for genotoxicity in a full battery of tests including an in vitro bacterial reverse mutation (Ames) assay, an in vitro micronucleus assay in human lymphocytes, a chromosomal aberration assay, and an in vivo bone marrow micronucleus assay in rats.”
Carcinogenicity
Not conducted; mouse and rat carcinogenicity studies are postmarketing requirements
“Two post-marketing requirements (PMRs) to conduct carcinogenicity studies in mice and rats were communicated to the Applicant.”
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
Rat EFD: early resorptions and kidney/testis visceral malformations at maternally toxic 75 mg/kg/day (~170x human AUC)
“Embryo-fetal toxicity (higher incidence of early resorptions, and visceral malformations of kidney and testes) occurred in rats at the maternally toxic dose of 75 mg/kg/day (approximately 170 times the human exposure based on the AUC at the highest recommended dose).”
Safety pharmacology
Assessed within repeat-dose studies; marginal 32 msec QTc prolongation in a single monkey at non-tolerable 40 mg/kg/day
“Safety pharmacology assessments conducted in the repeat-dose general toxicity studies resulted in marginal prolongation of the corrected QT interval (QTc) of 32 msec in a single male monkey administered the non-tolerable dose of 40 mg/kg/day.”
Genotox: Ames
Negative (vorasidenib and metabolite AGI-69460)
“Vorasidenib and its major circulating metabolite, AGI-69460, were negative for genotoxicity in a full battery of tests including an in vitro bacterial reverse mutation (Ames) assay, an in vitro micronucleus assay in human lymphocytes, a chromosomal aberration assay, and an in vivo bone marrow micronucleus assay in rats.”
Genotox: in vitro mammalian
Negative: in vitro micronucleus in human lymphocytes and chromosomal aberration assay
“Vorasidenib and its major circulating metabolite, AGI-69460, were negative for genotoxicity in a full battery of tests including an in vitro bacterial reverse mutation (Ames) assay, an in vitro micronucleus assay in human lymphocytes, a chromosomal aberration assay, and an in vivo bone marrow micronucleus assay in rats.”
Genotox: in vivo
Negative: rat bone marrow micronucleus
“Vorasidenib and its major circulating metabolite, AGI-69460, were negative for genotoxicity in a full battery of tests including an in vitro bacterial reverse mutation (Ames) assay, an in vitro micronucleus assay in human lymphocytes, a chromosomal aberration assay, and an in vivo bone marrow micronucleus assay in rats.”
Carcinogenicity model
Not conducted pre-approval; rodent (mouse and rat) carcinogenicity studies required postmarketing
“Carcinogenicity studies in mice and rats are warranted to determine the risk of carcinogenicity from vorasidenib for chronic use given the life expectancy of the proposed patient population.”
Carcinogenicity timing
Mouse and rat carcinogenicity studies not conducted before approval; postmarketing requirements
“Two post-marketing requirements (PMRs) to conduct carcinogenicity studies in mice and rats were communicated to the Applicant.”
hERG / QT
hERG IC50 >30 µM, >3500-fold unbound human Cmax at 40 mg daily
“Based on the results from clinical study AG881-C-004, an IC50 value of > 30 µM for vorasidenib for hERG current inhibition is > 3500-fold greater than the unbound human steady-state Cmax at the proposed therapeutic dose of 40 mg daily of vorasidenib (Cmax = 133 ng/ml).”
Same question, other small molecules
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 · CFTRVanzacaftor 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/TRKAmes negative; genotoxic via aneugenic mechanism in vitro (TK6 cells) and in vivo rat bone marrow micronucleus assay
Avmapki Fakzynja Co-pack
avutometinib and defactinib · RAF/MEK clamp; FAKDefactinib: Ames and chromosome aberration negative; positive in vitro and in vivo rat micronucleus (aneugenic)
Ayvakit
avapritinib · KIT/PDGFRAAmes negative; positive in vitro chromosome aberration; negative rat bone marrow micronucleus; overall non-genotoxic
Azstarys
serdexmethylphenidate and dexmethylphenidate · Dopamine/norepinephrine reuptakeNegative in Ames, in vitro human lymphocyte micronucleus, in vivo rat bone marrow micronucleus and rat comet assays
Balversa
erdafitinib · FGFR1-4Negative in Ames, in vitro micronucleus and in vivo rat bone marrow micronucleus assays
Barhemsys
amisulpride · Dopamine D2/D3 receptorNegative 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-2Negative 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 · SGLT2Negative in Ames, in vitro CHO chromosomal aberration, in vivo rat micronucleus and rat unscheduled DNA synthesis assays
Brexafemme
ibrexafungerp · Fungal glucan synthaseNegative 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 · BTKNegative 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 · IBATNegative in Ames, in vitro mouse lymphoma and in vivo rat micronucleus assays
Cabenuva
cabotegravir and rilpivirine · HIV-1 integrase; NNRTINegative in Ames and in vivo rat micronucleus assays
Camzyos
mavacamten · Cardiac myosinNegative in Ames, human lymphocyte clastogenicity and rat micronucleus assays
Caplyta
lumateperone · 5-HT2A / D2 receptorAmes and mouse lymphoma positive only with metabolic activation; negative rat micronucleus and Comet
Cardamyst
etripamil · L-type calcium channelNegative in Ames, in vitro chromosome aberration and in vivo rat micronucleus (IV) assays
Cibinqo
abrocitinib · JAK1Ames negative; aneugenic in in vitro micronucleus assay; negative in vivo rat micronucleus
Cobenfy
xanomeline and trospium · Muscarinic M1/M4 agonist; peripheral antagonistXanomeline negative in Ames, mouse lymphoma, rat hepatocyte UDS, CHO chromosome aberration and mouse micronucleus assays
Cosela
trilaciclib · CDK4/6Ames negative; negative for clastogenicity in human fibroblasts; increased micronuclei in human lymphocytes in vitro
Crenessity
crinecerfont · CRF1 receptorNegative in Ames, in vitro chromosomal aberration and in vivo rat bone marrow micronucleus assays
Cypsedo
cipepofol · GABA-A receptorNegative in Ames, in vitro chromosomal aberration and mouse bone marrow micronucleus assays
Daybue
trofinetide · IGF-1 tripeptide analogueNegative in Ames, in vitro CHO chromosomal aberration and in vivo mouse micronucleus assays
Dayvigo
lemborexant · Orexin OX1/OX2 receptorsNegative in Ames, mouse lymphoma TK and in vivo rat micronucleus assays
Defencath
taurolidine and heparin · Antimicrobial catheter lockTaurolidine positive in vitro (mouse lymphoma and Ames) regardless of metabolic activation; negative in vivo
Dojolvi
triheptanoin · Anaplerotic energy substrateNegative 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 kallikreinNegative in Ames, mouse lymphoma and in vivo rat micronucleus assays
Ensacove
ensartinib · ALKNegative in Ames, in vitro human lymphocyte chromosome aberration and in vivo rat micronucleus assays
Evrysdi
risdiplam · SMN2 splicingAmes 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 insertionNegative in Ames, in vitro chromosome aberration (human lymphocytes) and in vivo rat bone marrow micronucleus assays
Exxua
gepirone · 5-HT1A receptorNegative in Ames, CHO/HGPRT, hepatocyte DNA repair, rat micronucleus and 5-hour CHO chromosome aberration assays
Fabhalta
iptacopan · Complement factor BNot genotoxic or mutagenic in a battery of in vitro and in vivo assays
Fetroja
cefiderocol · Penicillin-binding proteinsAmes negative; chromosomal aberrations in vitro; negative in vivo rat micronucleus and liver comet assays
Fexinidazole
fexinidazole · Trypanosoma bruceiPositive in Ames; negative in in vitro human lymphocyte micronucleus and in vivo mouse bone marrow micronucleus assays
Filspari
sparsentan · Endothelin A / angiotensin II receptorsNegative in Ames, in vitro chromosomal aberration and in vivo rat micronucleus assays
Fotivda
tivozanib · VEGFR1-3Negative 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 · VEGFR1-3Negative in Ames, in vitro CHO chromosome aberration and in vivo rat micronucleus assays
Gavreto
pralsetinib · RETNegative in Ames, in vitro TK6 micronucleus and rat bone marrow micronucleus assays
Gemtesa
vibegron · β3-adrenergic receptorNegative in Ames, human lymphocyte chromosome aberration and rat bone marrow micronucleus assays
Gomekli
mirdametinib · MEK1/2Negative Ames; not clastogenic in vitro or in rat chromosome aberration assay; positive rat micronucleus
Grafapex
treosulfan · DNA alkylationMutagenic 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 · NHE3Negative in Ames, human lymphocyte chromosome aberration and in vivo micronucleus assays
Ibtrozi
taletrectinib · ROS1Negative in Ames and additional mutagenicity tests and in the rat bone marrow/liver micronucleus assay
Idvynso
doravirine and islatravir · NNRTI; NRTTIIslatravir: 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/SGLT2Negative 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 · JAK2Negative in Ames, in vitro CHO chromosomal aberration and rat micronucleus assays
Iqirvo
elafibranor · PPARα/δNegative 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 · PDE4BNegative 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 hydroxylaseNegative in Ames, in vitro human lymphocyte chromosomal aberration and in vivo rat bone marrow micronucleus assays
Jideytro
zidesamtinib · ROS1Positive in in vivo rat micronucleus assays; negative in Ames and in vitro TK6 clastogenicity assay
Joenja
leniolisib · PI3KδNegative in Ames, in vitro chromosomal aberration, in vitro TK6 micronucleus and in vivo rat micronucleus assays
Journavx
suzetrigine · NaV1.8Negative in Ames, in vitro TK6 micronucleus and in vivo rat bone marrow micronucleus assays
Kerendia
finerenone · Mineralocorticoid receptorNegative in Ames, in vitro chromosomal aberration and in vivo mouse micronucleus assays
Klisyri
tirbanibulin · Tubulin / SrcGenotoxic: Ames negative; positive in CHO chromosome aberration, mouse lymphoma and rat micronucleus assays
Komzifti
ziftomenib · Menin-KMT2ANegative in Ames, in vitro micronucleus and in vivo mouse bone marrow micronucleus assays
Koselugo
selumetinib · MEK1/2Not mutagenic or clastogenic in vitro; positive (aneugenic) mouse micronucleus at >160 mg/kg (~38x human Cmax)
Krazati
adagrasib · KRAS G12CNegative 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 cruziConsidered 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/JAK2Negative 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 kinasesAneugenic in in vitro TK6 micronucleus assay; Ames negative
Livdelzi
seladelpar · PPARδNegative 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 kinaseNegative in Ames and in vivo rat micronucleus; mutagenic without metabolic activation in mouse lymphoma assay; overall not genotoxic
Lumakras
sotorasib · KRAS G12CNegative in Ames and in vivo rat micronucleus and comet assays; some in vitro micronucleus induction
Lupkynis
voclosporin · CalcineurinNegative 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 · IBATNegative in Ames, in vitro CHO chromosome aberration and in vivo rat micronucleus assays
Lynkuet
elinzanetant · NK1/NK3 receptorsNegative 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 receptorNegative in Ames, mammalian cell assays and mouse and rat micronucleus assays
Miebo
perfluorohexyloctane · Tear film evaporation barrierNegative in Ames, in vitro human lymphocyte chromosome aberration and in vivo rat bone marrow micronucleus assays
Miplyffa
arimoclomol · Heat-shock response amplifierNegative in Ames, mouse lymphoma forward mutation and in vivo mouse micronucleus assays
Modeyso
dordaviprone · DRD2 antagonist / ClpP agonistNegative in Ames, in vitro and in vivo micronucleus assays
Myqorzo
aficamten · Cardiac myosinNegative in Ames, combined in vivo micronucleus and comet assays
Nereus
tradipitant · NK1 receptorNegative in Ames, in vitro human lymphocyte chromosomal aberration and mouse micronucleus assays
Nexletol
bempedoic acid · ATP citrate lyaseAmes negative; chromosome aberrations in human lymphocytes only with S9 at cytotoxic concentration
Nextstellis
drospirenone and estetrol · Estrogen / progestin receptorsEstetrol negative in Ames, mouse lymphoma, rat micronucleus and rat Comet assays (weight of evidence)
Nourianz
istradefylline · Adenosine A2A receptorNegative in Ames (4 assays), CHL chromosome aberration, mouse micronucleus and rat UDS assays
Nubeqa
darolutamide · Androgen receptorNegative 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 receptorNegative in Ames, in vitro chromosome aberration and rat bone marrow micronucleus assays
Nuzolvence
zoliflodacin · Bacterial topoisomerase IINegative in mouse lymphoma and rat micronucleus assays; Ames positive in TA102, consistent with mechanism
Ogsiveo
nirogacestat · Gamma secretaseNegative in Ames, in vitro human chromosome aberration and in vivo rat bone marrow micronucleus assays
Ohtuvayre
ensifentrine · PDE3/PDE4Negative 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/ACVR1Negative 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 receptorNegative in Ames and in vivo micronucleus; positive (mutagenic and clastogenic) in in vitro mouse lymphoma assay
Ongentys
opicapone · COMTNegative in Ames, in vitro chromosome aberration (human lymphocytes) and mouse micronucleus assays
Orgovyx
relugolix · GnRH receptorNegative in Ames, in vitro chromosome aberration and rat bone marrow micronucleus assays
Orladeyo
berotralstat · Plasma kallikreinNegative in Ames, in vitro human lymphocyte chromosomal aberration and rat micronucleus assays
Orlynvah
sulopenem etzadroxil and probenecid · Penicillin-binding proteinsAmes 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 agonistNegative in Ames and in vivo micronucleus; positive in vitro micronucleus (24-hour); overall non-genotoxic
Oxbryta
voxelotor · HbS polymerisationNegative in Ames, rat Comet and rat micronucleus assays
Palsonify
paltusotine · Somatostatin receptor 2Negative 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 · FGFR1-3Negative in Ames, in vitro chromosome aberration (human lymphocytes) and rat bone marrow micronucleus assays
Piqray
alpelisib · PI3KαNegative in Ames, in vitro micronucleus and chromosome aberration, and in vivo rat micronucleus assays
Pizensy
lactitol · Osmotic laxativeNot conducted by the applicant; published studies negative in Ames, chromosome aberration and in vivo mouse micronucleus tests
Ponvory
ponesimod · S1P1 receptorNegative in Ames, in vitro chromosomal aberration and rat micronucleus assays
Pretomanid
pretomanid · Mycobacterial cell wall / respirationNegative 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 reuptakeNegative in Ames, in vitro chromosomal aberration and rat bone marrow micronucleus assays
Qinlock
ripretinib · KIT/PDGFRANegative in Ames, in vitro chromosomal aberration, and in vivo rat micronucleus and comet assays
Qulipta
atogepant · CGRP receptorNegative in Ames, in vitro chromosomal aberration and in vivo rat bone marrow micronucleus assays
Quviviq
daridorexant · Orexin OX1/OX2 receptorsNegative in Ames, in vitro chromosome aberration (human lymphocytes) and in vivo rat micronucleus assays
Rapiblyk
landiolol · β1-adrenergic receptorNegative in Ames, in vitro mouse lymphoma TK and in vivo rat micronucleus assays
Rasonque
daraxonrasib · RAS(ON) multi-selectiveNegative 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 · RETNegative in Ames and in vitro micronucleus; positive in rat in vivo micronucleus at high doses
Revtorpyk
gedatolisib · PI3K/mTORNegative in Ames, human lymphocyte chromosomal aberration and rat bone marrow micronucleus assays
Revuforj
revumenib · Menin-KMT2ANegative in Ames, in vitro micronucleus and in vivo rat micronucleus assays
Reyvow
lasmiditan · 5-HT1F receptorNegative in Ames, in vitro chromosome aberration and mouse bone marrow micronucleus assays
Rezdiffra
resmetirom · Thyroid hormone receptor βNegative 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 · ROCK2Negative in Ames, in vitro chromosomal aberration and rat bone marrow micronucleus assays
Rezzayo
rezafungin · Fungal glucan synthaseNegative in Ames, in vitro mammalian clastogenicity and in vivo rat bone marrow micronucleus assays
Rhapsido
remibrutinib · BTKNegative in Ames, in vitro human lymphocyte micronucleus and in vivo rat micronucleus assays
Rinvoq
upadacitinib · JAK1Negative in Ames and in vivo rat micronucleus; in vitro chromosome aberration negative for structural, positive for numerical (polyploidy)
Romvimza
vimseltinib · CSF1RNegative in vivo rat bone marrow micronucleus and liver DNA strand-break assays; overall negative for genotoxicity
Rozlytrek
entrectinib · TRK/ROS1/ALKAmes 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 precursorNot genotoxic overall: Ames negative; in vitro chromosome aberration positive without (not with) metabolic activation; rat micronucleus and comet negative
Simtriyo
centanafadine · Triple monoamine reuptakeNegative in Ames, CHO chromosome aberration and rat in vivo micronucleus assays
Skyclarys
omaveloxolone · Nrf2 activatorNegative 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 · RARγNegative Ames and mouse micronucleus; in vitro chromosomal aberration positive only at cytotoxic concentrations
Sotyktu
deucravacitinib · TYK2Negative in Ames, in vitro chromosome aberration and in vivo rat micronucleus assays; major metabolites also negative
Sunlenca
lenacapavir · HIV-1 capsidNegative in Ames, in vitro human lymphocyte chromosome aberration and in vivo rat micronucleus assays
Sunosi
solriamfetol · Dopamine/norepinephrine reuptakeNegative in an adequate battery of genotoxicity assays
Tabrecta
capmatinib · METNegative 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 · EZH2Negative in Ames, in vitro micronucleus (human lymphocytes) and in vivo rat micronucleus assays
Tepmetko
tepotinib · METNegative in Ames, in vitro and in vivo micronucleus assays (parent and M506)
Trikafta
elexacaftor, tezacaftor and ivacaftor · CFTRElexacaftor negative in bacterial and mammalian in vitro assays and an in vivo chromosomal damage assay
Truqap
capivasertib · AKT1-3Negative in Ames and mouse lymphoma assays; positive (aneugenic) in rat bone marrow micronucleus; negative liver comet
Truseltiq
infigratinib · FGFR1-3Negative in Ames, in vitro human lymphocyte chromosome aberration and in vivo rat bone marrow micronucleus assays
Tryptyr
acoltremon · TRPM8 agonistNegative in Ames, in vitro chromosomal aberration (human lymphocytes) and rat micronucleus assays
Tryvio
aprocitentan · Endothelin A/B receptorsNegative in Ames, in vitro chromosomal aberration and in vivo rat micronucleus assays
Tukysa
tucatinib · HER2Negative in Ames, in vitro chromosome aberration and mouse bone marrow micronucleus assays
Turalio
pexidartinib · CSF1RNegative in Ames, in vitro chromosome aberration (human lymphocytes) and rat bone marrow micronucleus assays
Ubrelvy
ubrogepant · CGRP receptorNegative in Ames, in vitro chromosomal aberration and in vivo rat bone marrow micronucleus assays
Ukoniq
umbralisib · PI3Kδ / CK1εNegative in Ames, in vitro TK6 micronucleus and in vivo mouse micronucleus assays
Utebzi
tebipenem pivoxil · Penicillin-binding proteinsProdrug positive in vitro (mammalian gene mutation, CHO chromosomal aberration); negative in mouse bone marrow micronucleus
Vafseo
vadadustat · HIF prolyl hydroxylaseAmes negative; clastogenic in two in vitro assays; negative in vivo rat comet and chromosome aberration assays; not genotoxic overall
Vanflyta
quizartinib · FLT3Positive in Ames; negative in mouse lymphoma, human lymphocyte chromosome aberration and rat micronucleus assays
Vanrafia
atrasentan · Endothelin A receptorNegative in Ames, in vitro chromosomal aberration and in vivo mouse micronucleus assays
Veklury
remdesivir · SARS-CoV-2 RNA polymeraseNegative in Ames, human lymphocyte chromosome aberration and rat micronucleus assays
Velsipity
etrasimod · S1P1/S1P4/S1P5 receptorsNegative in Ames, human lymphocyte chromosomal aberration and rat micronucleus assays
Veozah
fezolinetant · Neurokinin-3 receptorNegative 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 cyclaseNegative in Ames, mouse lymphoma and rat and mouse micronucleus assays
Vivjoa
oteseconazole · Fungal CYP51Negative 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/FLT3Negative 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
Voydeya
danicopan · Complement factor DNegative in Ames, in vitro human lymphocyte micronucleus and in vivo rat micronucleus assays
Vtama
tapinarof · Aryl hydrocarbon receptorNegative 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 receptorNegative 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-2αNegative 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-ANegative in Ames, mouse lymphoma and rat bone marrow micronucleus assays
Xdemvy
lotilaner · Mite GABA-Cl channelNegative in Ames, in vitro chromosome aberration (human lymphocytes) and rat micronucleus assays
Xeglyze
abametapir · Lice metalloproteinasesAmes 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 proteaseNegative in Ames, in vitro TK6 micronucleus and in vivo rat micronucleus assays
Xolremdi
mavorixafor · CXCR4Negative in Ames, in vitro chromosome aberration (human lymphocytes) and rat micronucleus assays
Xpovio
selinexor · XPO1Negative in Ames, in vitro human lymphocyte cytogenetic and in vivo rat micronucleus assays
Zavzpret
zavegepant · CGRP receptorNegative 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 insertionNegative 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 receptorOzanimod 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 proteinsNegative in vivo (micronucleus and rat liver UDS), reducing concern over clastogenic signals in vitro
Zokinvy
lonafarnib · FarnesyltransferaseNegative 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