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Compound Detail

CHEMBL3989958

IVOSIDENIB
💊 Approved Drug
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💊 Approved Drug
N#Cc1ccnc(N2C(=O)CC[C@H]2C(=O)N(c2cncc(F)c2)[C@H](C(=O)NC2CC(F)(F)C2)c2ccccc2Cl)c1
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL3989958
Name IVOSIDENIB
Phase Approved
Structure Type MOL
InChI Key WIJZXSAJMHAVGX-DHLKQENFSA-N
Therapeutic ✓ Yes

Known Names

AG-120 Ivosidenib Tibsovo
4
Targets
47
Activities
3
Assay Types
7
PK Parameters
20
Publications
3
Known Names
11
Indications
1
Mechanisms

Molecular Properties

583.0
MW (Da)
4.32
ALogP
6
HBA
1
HBD
119.3
PSA (Ų)
0.44
QED
1
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2018
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Black Box Warning First in Class
USAN Stem -sidenib
USAN Year 2017

Extended Properties

Molecular Formula C28H22ClF3N6O3
MW 582.97
Aromatic Rings 3
Heavy Atoms 41
NP-Likeness -1.57

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Isocitrate dehydrogenase [NADP] cytoplasmic inhibitor INHIBITOR Isocitrate dehydrogenase [NADP] cytoplasmic ✓ ✓

Indications

Cholangiocarcinoma Leukemia, Myeloid, Acute Biliary Tract Neoplasms Myelodysplastic Syndromes Chondrosarcoma Neoplasms Paraganglioma Carcinoma, Pancreatic Ductal Leukemia Leukemia, Myeloid Liver Diseases

ATC Classification

L01XM02
ivosidenib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Drug Warnings

Black Box Warning
carcinogenicity
Country: United States

Activity Summary

IC50 39 meas. best 8.46
Kd 6 meas. best 6.38
EC50 2 meas. best 7.9

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Isocitrate dehydrogenase [NADP] cytoplasmic
CHEMBL2007625
 IC50 8.46 7.3892 3.5 25
HT-1080
CHEMBL614580
 IC50 8.1 8.1 8.0 2
Isocitrate dehydrogenase [NADP] cytoplasmic
CHEMBL2007625
 EC50 7.9 7.735 12.5 2
U-87 MG
CHEMBL614247
 IC50 7.72 5.8911 19.0 9
Isocitrate dehydrogenase [NADP] cytoplasmic
CHEMBL2007625
 Kd 6.38 5.4517 420.0 6
Isocitrate dehydrogenase [NADP], mitochondrial
CHEMBL3991501
 IC50 5.14 5.14 7200.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 6505.95 ng.hr.mL-1 Mus musculus
AUC 1732.59 ng.hr.mL-1 Mus musculus
CL 9.0 mL.min-1.kg-1 Mus musculus
Cmax 2264.0 nM Mus musculus
F 80.0 % Mus musculus
T1/2 3.5 hr Mus musculus
T1/2 2.5 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 3.5 nM 8.46 Inhibition of recombinant human C-terminal His8-tagged IDH1 R132H mutant express... 31561044
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 4.5 nM 8.35 Inhibition of IDH1 R132H mutant (unknown origin) expressed in Escherichia coli B... 37209613
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 4.9 nM 8.31 Inhibition of recombinant IDH1 R132H mutant (unknown origin) expressed in Escher... 36952395
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 7.5 nM 8.12 Inhibition of IDH1 R132C mutant in human HT1080 cells assessed as reduction in 2... 29079473
HT-1080 IC50 = 8.0 nM 8.1 Antiproliferative activity against human HT-1080 cells harboring IDH1 R132H muta... 37235998
HT-1080 IC50 = 8.0 nM 8.1 Antiproliferative activity against human HT-1080 cells assessed as cell growth i... 37235998
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 12.0 nM 7.92 Biochemical Assay: Compound 1 was not initially reported as having the greatest ... -
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 12.0 nM 7.92 In Vitro Biochemical Assay: Please see paper. -
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 12.0 nM 7.92 Cell Based Assays: The cellular potency of Compound 1 in suppressing intracellul... -
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 12.0 nM 7.92 Inhibition of N-terminal His-tagged wild type IDH1 R132H mutant (40 to 452 resid... 37235998
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 12.0 nM 7.92 Inhibition of IDH1 R132H mutant (unknown origin) 37235998
Isocitrate dehydrogenase [NADP] cytoplasmic EC50 = 12.47 nM 7.9 Inhibition of C-terminal NanoLuc 86b-tagged IDH1 R132H (unknown origin) expresse... 33822623
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 13.0 nM 7.89 Inhibition of IDH1 R132C mutant (unknown origin) 37235998
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 13.0 nM 7.89 Biochemical Assay: Compound 1 was not initially reported as having the greatest ... -
U-87 MG IC50 = 19.0 nM 7.72 Antiproliferative activity against human U-87 MG cells assessed as reduction in ... 37235998
U-87 MG IC50 = 19.0 nM 7.72 Antiproliferative activity against human U-87 MG cells harboring IDH1 R132H muta... 37235998
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 19.0 nM 7.72 Inhibition of IDH1 R132C mutant (unknown origin) expressed in Escherichia coli B... 37209613
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 19.0 nM 7.72 Inhibition of IDH1 R132H mutant (unknown origin) 29079473
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 23.0 nM 7.64 Inhibition of recombinant human C-terminal His8-tagged IDH1 R132C mutant express... 31561044
Isocitrate dehydrogenase [NADP] cytoplasmic IC50 = 25.4 nM 7.59 Inhibition of IDH1 R132C mutant in human HT1080 cells assessed as reduction in 2... 31561044

Literature References

PubMed DOI Target Context # Activities
38651495 10.1021/acs.jmedchem.3c02482 U-87 MG 19
36952395 10.1021/acs.jmedchem.3c00203 Isocitrate dehydrogenase [NADP] cytoplasmic 18
31561044 10.1016/j.ejmech.2019.111694 ADMET 11
29847930 10.1021/acs.jmedchem.8b00159 ADMET 6
37235998 10.1016/j.ejmech.2023.115464 Isocitrate dehydrogenase [NADP] cytoplasmic 5
31561044 10.1016/j.ejmech.2019.111694 Isocitrate dehydrogenase [NADP] cytoplasmic 4
33822623 10.1021/acs.jmedchem.1c00019 Isocitrate dehydrogenase [NADP] cytoplasmic 4
37209613 10.1016/j.ejmech.2023.115411 Isocitrate dehydrogenase [NADP] cytoplasmic 4
38651495 10.1021/acs.jmedchem.3c02482 Isocitrate dehydrogenase [NADP] cytoplasmic 3
37209613 10.1016/j.ejmech.2023.115411 Isocitrate dehydrogenase [NADP], mitochondrial 3
37468498 10.1038/s41467-023-40064-9 Thromboxane A2 receptor 2
29079473 10.1016/j.bmcl.2017.10.029 Isocitrate dehydrogenase [NADP] cytoplasmic 2
37468498 10.1038/s41467-023-40064-9 Prostaglandin G/H synthase 1 2
37468498 10.1038/s41467-023-40064-9 Alpha-1A adrenergic receptor 2
37235998 10.1016/j.ejmech.2023.115464 U-87 MG 2
- 10.6019/CHEMBL4808148 Histone deacetylase 6 2
- 10.6019/CHEMBL4495565 SARS-CoV-2 2
37235998 10.1016/j.ejmech.2023.115464 HT-1080 2
37468498 10.1038/s41467-023-40064-9 Muscarinic acetylcholine receptor M1 2
37235998 10.1016/j.ejmech.2023.115464 Unchecked 2

Data from ChEMBL 36 via Core Engine