Ivosidenib - CAS 1448347-49-6
Catalog number: B0084-474585
Category: Inhibitor
Not Intended for Therapeutic Use. For research use only.
Molecular Formula:
C28H22ClF3N6O3
Molecular Weight:
582.968
COA:
Inquire
Targets:
Isocitrate Dehydrogenase (IDH)
Description:
Ivosidenib is an oral inhibitor that specifically inhibits a mutated form of IDH1 in the cytoplasm, which blocks the proliferation of tumor cells expressing IDH1.
Ordering Information
Catalog Number Size Price Stock Quantity
B0084-474585 100 mg $198 In stock
Bulk Inquiry
Related CAS:
1448346-63-1 (racemic form)
Appearance:
Solid Powder
Synonyms:
AG-120; AG120; (2S)-N-[(1S)-1-(2-chlorophenyl)-2-[(3,3-difluorocyclobutyl)amino]-2-oxoethyl]-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide
Solubility:
Soluble in DMSO.
Storage:
Store in a cool and dry place and at 0 - 4℃ for short term (days to weeks) or -65℃ for long term (months to years).
MSDS:
Inquire
Shelf Life:
2 years
Boiling Point:
854.3±65.0 °C at 760 mmHg
Density:
1.51±0.1 g/cm3
InChIKey:
WIJZXSAJMHAVGX-DHLKQENFSA-N
InChI:
InChI=1S/C28H22ClF3N6O3/c29-21-4-2-1-3-20(21)25(26(40)36-18-11-28(31,32)12-18)37(19-10-17(30)14-34-15-19)27(41)22-5-6-24(39)38(22)23-9-16(13-33)7-8-35-23/h1-4,7-10,14-15,18,22,25H,5-6,11-12H2,(H,36,40)/t22-,25-/m0/s1
Canonical SMILES:
C1CC(=O)N(C1C(=O)N(C2=CC(=CN=C2)F)C(C3=CC=CC=C3Cl)C(=O)NC4CC(C4)(F)F)C5=NC=CC(=C5)C#N
1.Targeting isocitrate dehydrogenase (IDH) in cancer.
Fujii T;Khawaja MR;DiNardo CD;Atkins JT;Janku F Discov Med. 2016 May;21(117):373-80.
Isocitrate dehydrogenase (IDH) is an essential enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle. Recurrent mutations in IDH1 or IDH2 are prevalent in several cancers including glioma, acute myeloid leukemia (AML), cholangiocarcinoma and chondrosarcoma. The mutated IDH1 and IDH2 proteins have a gain-of-function, neomorphic activity, catalyzing the reduction of α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG) by NADPH. Cancer-associated IDH mutations block normal cellular differentiation and promote tumorigenesis via the abnormal production of the oncometabolite 2-HG. High levels of 2-HG have been shown to inhibit α-KG dependent dioxygenases, including histone and deoxyribonucleic acid (DNA) demethylases, which play a key role in regulating the epigenetic state of cells. Current targeted inhibitors of IDH1 (AG120, IDH305), IDH2 (AG221), and pan-IDH1/2 (AG881) selectively inhibit mutant IDH protein and induce cell differentiation in in vitro and in vivo models. Preliminary results from phase I clinical trials with IDH inhibitors in patients with advanced hematologic malignancies have demonstrated an objective response rate ranging from 31% to 40% with durable responses (>1 year) observed.
2.Acquired resistance to IDH inhibition through trans or cis dimer-interface mutations.
Intlekofer AM;Shih AH;Wang B;Nazir A;Rustenburg AS;Albanese SK;Patel M;Famulare C;Correa FM;Takemoto N;Durani V;Liu H;Taylor J;Farnoud N;Papaemmanuil E;Cross JR;Tallman MS;Arcila ME;Roshal M;Petsko GA;Wu B;Choe S;Konteatis ZD;Biller SA;Chodera JD;Thompson CB;Levine RL;Stein EM Nature. 2018 Jul;559(7712):125-129. doi: 10.1038/s41586-018-0251-7. Epub 2018 Jun 27.
Somatic mutations in the isocitrate dehydrogenase 2 gene (IDH2) contribute to the pathogenesis of acute myeloid leukaemia (AML) through the production of the oncometabolite 2-hydroxyglutarate (2HG);1-8;. Enasidenib (AG-221) is an allosteric inhibitor that binds to the IDH2 dimer interface and blocks the production of 2HG by IDH2 mutants;9,10;. In a phase I/II clinical trial, enasidenib inhibited the production of 2HG and induced clinical responses in relapsed or refractory IDH2-mutant AML;11;. Here we describe two patients with IDH2-mutant AML who had a clinical response to enasidenib followed by clinical resistance, disease progression, and a recurrent increase in circulating levels of 2HG. We show that therapeutic resistance is associated with the emergence of second-site IDH2 mutations in trans, such that the resistance mutations occurred in the IDH2 allele without the neomorphic R140Q mutation. The in trans mutations occurred at glutamine 316 (Q316E) and isoleucine 319 (I319M), which are at the interface where enasidenib binds to the IDH2 dimer. The expression of either of these mutant disease alleles alone did not induce the production of 2HG; however, the expression of the Q316E or I319M mutation together with the R140Q mutation in trans allowed 2HG production that was resistant to inhibition by enasidenib.
3.Therapeutic choices after hypomethylating agent resistance for myelodysplastic syndromes.
Montalban-Bravo G;Garcia-Manero G;Jabbour E Curr Opin Hematol. 2018 Mar;25(2):146-153. doi: 10.1097/MOH.0000000000000400.
PURPOSE OF REVIEW: ;Hypomethylating agents (HMAs) are the standard of care for patients with myelodysplastic syndromes (MDS). Although these agents induce responses in up to 40% of patients, most patients ultimately experience loss of response. The purpose of this review is to provide an overview of the different therapies under development for MDS after HMA therapy.;RECENT FINDINGS: ;Recent advances in the understanding of MDS pathogenesis have led to the development of new potential therapies after HMA failure. Newer HMAs, less susceptible to in-vivo deamination, such as guadecitabine or ASTX727 have shown activity. Alterations of immune checkpoints in MDS have led to multiple clinical trials evaluating the activity of monoclonal antibodies targeting these proteins (pembrolizumab, nivolumab, ipilimumab). Different combinations and new formulations of cytotoxic agents, such as clofarabine or CPX-351, are newer options for specific subsets of patients. Finally, targeted agents inhibiting multiple kinases (rigosertib), BCL2 (venetoclax) or mutant IDH1 (ivosidenib), IDH2 (enasidenib), FLT3 (sorafenib, midostaurin) or spliceosome components (H3B-8800) are other novel options.;SUMMARY: ;Despite the poor prognosis associated with HMA failure, clinical trials, new cytotoxic agents and allogeneic stem-cell transplantation, can offer therapeutic opportunities for these patients for whom there is no standard of care.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related Isocitrate Dehydrogenase (IDH) Products


CAS 1429176-69-1 Mutant IDH1-IN-2

Mutant IDH1-IN-2
(CAS: 1429176-69-1)

Mutant IDH1-IN-2, aslo called as SCHEMBL14831158, is an inhibitor of mutant IDH protein. It is developed for the treatment of diseases associated with such muta...

CAS 1816331-63-1 GSK321

GSK321
(CAS: 1816331-63-1)

GSK321 is a highly potent, selective inhibitor of mutant IDH1 enzymes, with IC50= 4.6 nM against R132H, 3.8 nM against R132C and 2.9 nM against R132G. GSK321 st...

CAS 1355326-35-0 AGI-5198

AGI-5198
(CAS: 1355326-35-0)

AGI-5198 is the first highly potent and selective inhibitor of IDH1 R132H/R132C mutants with IC50 of 0.07 μM/0.16 μM.

CAS 1448347-49-6 Ivosidenib

Ivosidenib
(CAS: 1448347-49-6)

Ivosidenib is an oral inhibitor that specifically inhibits a mutated form of IDH1 in the cytoplasm, which blocks the proliferation of tumor cells expressing IDH...

CAS 1432660-47-3 AGI-6780

AGI-6780
(CAS: 1432660-47-3)

AGI-6780 is an IDH2 inhibitor that potently and selectively inhibits the tumor-associated mutant IDH2/R140Q with IC50 of 23±1.7 nM. AGI-6780 is less potent agai...

CAS 50405-58-8 TC-E 5008

TC-E 5008
(CAS: 50405-58-8)

TC-E 5008 is a selective and cancer-associated mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor (Ki = 120-190 nM), displaying >60-fold selectivity for mIDH1 ...

CAS 1650550-25-6 Enasidenib mesylate

Enasidenib mesylate
(CAS: 1650550-25-6)

Enasidenib mesylate is a first-in-class, oral, potent, reversible, selective inhibitor of the IDH2 mutant enzymes indicated for the treatment of adult patients ...

CAS 1446502-11-9 Enasidenib

Enasidenib
(CAS: 1446502-11-9)

Enasidenib, aslo known as AG-221 and CC-90007, is a potent and selective IDH2 inhibitor with potential anticancer activity (IDH2 = Isocitrate dehydrogenase 2).

AG-120
(CAS: 1448346-63-1)

AG-120 is an orally available inhibitor of isocitrate dehydrogenase type 1 (IDH1), with potential antineoplastic activity.

CAS 1429180-08-4 SCHEMBL14831541

SCHEMBL14831541
(CAS: 1429180-08-4)

SCHEMBL14831541, also called as Mutant IDH1 inhibitor, is an inhibitor of mutant IDH1 which is key enzymes found in cellular metabolism.

CAS 1355326-21-4 Mutant IDH1-IN-1

Mutant IDH1-IN-1
(CAS: 1355326-21-4)

Mutant IDH1-IN-1, a mutant IDH1 R132H inhibitor, could be used in some biological studies.

CAS 1816331-66-4 GSK864

GSK864
(CAS: 1816331-66-4)

GSK864 is a cell penetrant, selective allosteric inhibitor of isocitrate dehydrogenase 1 (IDH1) mutant with IC50 values of 8.8, 15.2 and 16.6 nM for IDH1 mutant...

CAS 6147-11-1 alpha-Mangostin

alpha-Mangostin
(CAS: 6147-11-1)

Alpha-mangostin, a prenylated xanthone derivative from Mangosteen, Garcinia mangostana L. (Clusiaceae), has shown to possess diverse pharmacological activities ...

Chemical Structure

CAS 1448347-49-6 Ivosidenib

Quick Inquiry

Verification code

Featured Items