Vorasidenib

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C14H13ClF6N6
Molecular Weight	414.737
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

C[C@@H](NC1=NC(=NC(N[C@H](C)C(F)(F)F)=N1)C2=CC=CC(Cl)=N2)C(F)(F)F

InChI

InChIKey=QCZAWDGAVJMPTA-RNFRBKRXSA-N

InChI=1S/C14H13ClF6N6/c1-6(13(16,17)18)22-11-25-10(8-4-3-5-9(15)24-8)26-12(27-11)23-7(2)14(19,20)21/h3-7H,1-2H3,(H2,22,23,25,26,27)/t6-,7-/m1/s1

HIDE SMILES / InChI

Description

Vorasidenib (also known as AG 881) was developed as an isocitrate dehydrogenase (IDH) type 1 in the cytoplasm and type 2 in the mitochondria, with potential antineoplastic activity. It is known that IDH is an essential enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle. Isocitrate dehydrogenases 1 and 2 (IDH1/2) are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid cycle. Vorasidenib participated in phase I clinical trials in patients with advanced hematologic malignancies and in gliomas.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Isocitrate dehydrogenase [NADP], mitochondrial 6	Inhibitor 8,504
Isocitrate dehydrogenase [NADP] cytoplasmic 5	Inhibitor 8,504

Conditions

Condition	Modality	Highest Phase	Product
Acute myeloid leukemia 141	Primary	Phase I 438	Unknown
Myelodysplastic syndromes 61	Primary	Phase I 438	Unknown
Glioma 25	Primary	Phase I 438	Unknown

C_max

Value	Dose	Analyte	Population
26.7 ng/mL	10 mg single, oral	VORASIDENIB plasma	Homo sapiens
21.8 ng/mL	25 mg single, oral	VORASIDENIB plasma	Homo sapiens
70.2 ng/mL	50 mg single, oral	VORASIDENIB plasma	Homo sapiens
104 ng/mL	100 mg single, oral	VORASIDENIB plasma	Homo sapiens
178 ng/mL	200 mg single, oral	VORASIDENIB plasma	Homo sapiens
302 ng/mL	300 mg single, oral	VORASIDENIB plasma	Homo sapiens
45.7 ng/mL	10 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
66.5 ng/mL	25 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
195 ng/mL	50 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
223 ng/mL	100 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
412 ng/mL	200 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
493 ng/mL	300 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
47 ng/mL	25 mg single, oral	VORASIDENIB plasma	Homo sapiens
81.4 ng/mL	50 mg single, oral	VORASIDENIB plasma	Homo sapiens
91.9 ng/mL	100 mg single, oral	VORASIDENIB plasma	Homo sapiens
226 ng/mL	200 mg single, oral	VORASIDENIB plasma	Homo sapiens
226 ng/mL	200 mg 2 times / day multiple, oral	VORASIDENIB plasma	Homo sapiens
449 ng/mL	300 mg single, oral	VORASIDENIB plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
452 ng × h/mL	10 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
940 ng × h/mL	25 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
2282 ng × h/mL	50 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
2476 ng × h/mL	100 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
7020 ng × h/mL	200 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
7020 ng × h/mL	300 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
84.4 ng × h/mL	10 mg single, oral	VORASIDENIB plasma	Homo sapiens
103 ng × h/mL	25 mg single, oral	VORASIDENIB plasma	Homo sapiens
265 ng × h/mL	50 mg single, oral	VORASIDENIB plasma	Homo sapiens
496 ng × h/mL	100 mg single, oral	VORASIDENIB plasma	Homo sapiens
814 ng × h/mL	200 mg single, oral	VORASIDENIB plasma	Homo sapiens
1540 ng × h/mL	300 mg single, oral	VORASIDENIB plasma	Homo sapiens
284 ng × h/mL	10 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
507 ng × h/mL	25 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
1310 ng × h/mL	50 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
1500 ng × h/mL	100 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
3160 ng × h/mL	200 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
4010 ng × h/mL	300 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
260 ng × h/mL	25 mg single, oral	VORASIDENIB plasma	Homo sapiens
409 ng × h/mL	50 mg single, oral	VORASIDENIB plasma	Homo sapiens
378 ng × h/mL	100 mg single, oral	VORASIDENIB plasma	Homo sapiens
990 ng × h/mL	200 mg single, oral	VORASIDENIB plasma	Homo sapiens
990 ng × h/mL	200 mg 2 times / day multiple, oral	VORASIDENIB plasma	Homo sapiens
1860 ng × h/mL	300 mg single, oral	VORASIDENIB plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
67.2 h	10 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
67.2 h	25 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
67.2 h	50 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
67.2 h	100 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
67.2 h	200 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
67.2 h	300 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
68.7 h	10 mg single, oral	VORASIDENIB plasma	Homo sapiens
87.3 h	25 mg single, oral	VORASIDENIB plasma	Homo sapiens
46.9 h	50 mg single, oral	VORASIDENIB plasma	Homo sapiens
64.7 h	100 mg single, oral	VORASIDENIB plasma	Homo sapiens
55.1 h	200 mg single, oral	VORASIDENIB plasma	Homo sapiens
47.4 h	300 mg single, oral	VORASIDENIB plasma	Homo sapiens
68.7 h	10 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
87.3 h	25 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
46.9 h	50 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
64.7 h	100 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
55.1 h	200 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
47.4 h	300 mg 1 times / day steady-state, oral	VORASIDENIB plasma	Homo sapiens
176 h	25 mg single, oral	VORASIDENIB plasma	Homo sapiens
54.1 h	50 mg single, oral	VORASIDENIB plasma	Homo sapiens
45.5 h	100 mg single, oral	VORASIDENIB plasma	Homo sapiens
51 h	200 mg single, oral	VORASIDENIB plasma	Homo sapiens
51 h	200 mg 2 times / day multiple, oral	VORASIDENIB plasma	Homo sapiens
78.8 h	300 mg single, oral	VORASIDENIB plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
6%			VORASIDENIB plasma	Homo sapiens

PubMed

PubMed

Show entries

Title	Date	PubMed
The Evolving Landscape in the Development of Isocitrate Dehydrogenase Mutant Inhibitors.	2016	27292784
Targeting isocitrate dehydrogenase (IDH) in cancer.	2016 May	27355333

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Sample Use Guides

In Vivo Use Guide

oral doses of AG-881 to determine maximum tolerated dose (MTD) and/or the recommended Phase II dose

Route of Administration: Oral

Show entries

Name

Type

Language

Vorasidenib

Official Name

English

1,3,5-Triazine-2,4-diamine, 6-(6-chloro-2-pyridinyl)-N<SUP>2</SUP>,N<SUP>4</SUP>-bis[(1R)-2,2,2-trifluoro-1-methylethyl]-

Preferred Name

English

vorasidenib [INN]

Common Name

English

AG-881

Code

English

Vorasidenib [WHO-DD]

Common Name

English

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Classification Tree

Code System

Code

Enzyme Inhibitor

NCI_THESAURUS

C137826

Designated

FDA ORPHAN DRUG

649318

Antineoplastic Protein Inhibitor

NCI_THESAURUS

C129825

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Code System

Code

Type

Description

INN

10525

PRIMARY

NCI_THESAURUS

C152914

PRIMARY

SMS_ID

100000184129

PRIMARY

CAS

1644545-52-7

PRIMARY

FDA UNII

789Q85GA8P

PRIMARY

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ACTIVE MOIETY


					789Q85GA8P

Vorasidenib

SALT/SOLVATE (PARENT)


					W4XG3EQK7B

Vorasidenib hemicitric acid

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

PubMed

Sample Use Guides

C_max

T_1/2

F_unbound