OBATOCLAX

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H19N3O
Molecular Weight	317.3844
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC(=N\C1=C/C2=C(C)C=C(C)N2)C3=CC4=CC=CC=C4N3

InChI

InChIKey=RFTSSZJZXOSICM-GRSHGNNSSA-N

InChI=1S/C20H19N3O/c1-12-8-13(2)21-16(12)10-19-20(24-3)11-18(23-19)17-9-14-6-4-5-7-15(14)22-17/h4-11,21-22H,1-3H3/b19-10-

HIDE SMILES / InChI

Molecular Formula	C20H19N3O
Molecular Weight	317.3844
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22324354 | https://www.ncbi.nlm.nih.gov/pubmed/18040043
Curator's Comment: Description was created based on several sources, including http://en.pharmacodia.com/web/drug/1_2376.html | http://adisinsight.springer.com/drugs/800013657

Obatoclax (GX15-070) is a novel BH3 mimetic pan Bcl- 2 inhibitor. The clinically studied formulation is as obatoclax mesylate (Box 1), a salt. It is only under study as an intravenous preparation. It functions to block BH3-mediated binding of Bcl-2, Bcl-XL, Mcl-1 and A1 to Bax and Bak. Bax and Bak thus are unopposed and able to dimerize to allow initiation of intrinsic apoptosis. Preclinically, obatoclax has been shown to reverse inhibition of Bax or Bak by Bcl-2, Bcl-XL, Bcl-w and Mcl-1. Obatoclax was discovered by Gemin X, which was acquired by Cephalon, which has since been acquired by Teva Pharmaceuticals. Obatoclax had been in phase III clinical trials by Gemin X Biotechnologies (subsidiary of Teva) for the treatment of non-small lung cancer (NSCLC). The compound received orphan drug designation in the U.S. in 2004 for the treatment of chronic lymphocytic leukemia (CLL). However, Teva discontinued the development of obatoclax in 2013.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Apoptosis regulator Bcl-2 19 Target ID: CHEMBL4860 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22195752	Inhibitor 8297		0.22 µM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Small-cell lung cancer 41 Sources: http://adisinsight.springer.com/drugs/800013657 https://clinicaltrials.gov/ct2/show/NCT01563601	Primary	Phase III 656	Unknown Approved Use Unknown
Hodgkin's lymphoma 34 Sources: http://adisinsight.springer.com/drugs/800013657 https://clinicaltrials.gov/ct2/show/NCT00359892	Primary	Phase II 1132	Unknown Approved Use Unknown
Leukemia 87 Sources: http://adisinsight.springer.com/drugs/800013657 https://clinicaltrials.gov/ct2/show/NCT00918931	Primary	Phase II 1132	Unknown Approved Use Unknown
Myelofibrosis 15 Sources: https://clinicaltrials.gov/ct2/show/NCT00360035	Primary	Phase II 1132	Unknown Approved Use Unknown
Systemic mastocytosis 2 Sources: http://adisinsight.springer.com/drugs/800013657 https://clinicaltrials.gov/ct2/show/NCT00918931	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
92.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18931344	40 mg/m² 1 times / 3 weeks multiple, intravenous dose: 40 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	OBATOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
27.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20538761	1.25 mg/m² 1 times / week multiple, intravenous dose: 1.25 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	OBATOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
114.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20538761	20 mg/m² 1 times / week multiple, intravenous dose: 20 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	OBATOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
33.46 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20538761	7 mg/m² 1 times / week multiple, intravenous dose: 7 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	OBATOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
155 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20538761	28 mg/m² 1 times / week multiple, intravenous dose: 28 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	OBATOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
277 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18931344	40 mg/m² 1 times / 3 weeks multiple, intravenous dose: 40 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	OBATOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
34.37 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20538761	1.25 mg/m² 1 times / week multiple, intravenous dose: 1.25 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	OBATOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
401 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20538761	20 mg/m² 1 times / week multiple, intravenous dose: 20 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	OBATOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
55.01 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20538761	7 mg/m² 1 times / week multiple, intravenous dose: 7 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	OBATOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
599 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20538761	28 mg/m² 1 times / week multiple, intravenous dose: 28 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	OBATOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
59.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18931344	40 mg/m² 1 times / 3 weeks multiple, intravenous dose: 40 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	OBATOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11.66 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20538761	1.25 mg/m² 1 times / week multiple, intravenous dose: 1.25 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	OBATOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
28.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20538761	20 mg/m² 1 times / week multiple, intravenous dose: 20 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	OBATOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
45.46 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20538761	7 mg/m² 1 times / week multiple, intravenous dose: 7 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	OBATOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
39 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20538761	28 mg/m² 1 times / week multiple, intravenous dose: 28 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	OBATOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
60 mg 1 times / day multiple, intravenous Highest studied dose Dose: 60 mg, 1 times / day Route: intravenous Route: multiple Dose: 60 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25285531 Page: p.6	unhealthy, ADULT n = 5 Health Status: unhealthy Condition: acute myeloid leukemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/25285531 Page: p.6	Sources: https://pubmed.ncbi.nlm.nih.gov/25285531 Page: p.6
20 mg 1 times / day multiple, intravenous MTD Dose: 20 mg, 1 times / day Route: intravenous Route: multiple Dose: 20 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25285531 Page: p.4, 6	unhealthy, ADULT n = 10 Health Status: unhealthy Condition: acute myeloid leukemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/25285531 Page: p.4, 6	Sources: https://pubmed.ncbi.nlm.nih.gov/25285531 Page: p.4, 6
1.25 mg/m2 1 times / week multiple, intravenous MTD Dose: 1.25 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 1.25 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/20538761 Page: p.5,13	unhealthy, ADULT n = 1 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: unknown Food Status: UNKNOWN Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20538761 Page: p.5,13	Sources: https://pubmed.ncbi.nlm.nih.gov/20538761 Page: p.5,13
20 mg/m2 1 times / week multiple, intravenous MTD Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/20538761 Page: p.5	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/20538761 Page: p.5	Sources: https://pubmed.ncbi.nlm.nih.gov/20538761 Page: p.5
30 mg 1 times / day multiple, intravenous Studied dose Dose: 30 mg, 1 times / day Route: intravenous Route: multiple Dose: 30 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25285531 Page: p.4, 6	unhealthy, ADULT n = 3 Health Status: unhealthy Condition: acute myeloid leukemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/25285531 Page: p.4, 6	DLT: Somnolence, Confusion... Other AEs: Ataxia, Somnolence... Dose limiting toxicities: Somnolence (grade 3, 33.3%) Confusion (grade 3, 33.3%) Ataxia (grade 3, 33.3%) Other AEs: Ataxia (grade 1-2, 33.3%) Somnolence (grade 1, 33.3%) Euphoria (grade 1-2, 66.7%) Speech disorder (grade 1-2, 33.3%) Mood alteration NOS (grade 1-2, 33.3%) Dizziness (grade 1-2, 33.3%) Confusion (grade 1, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/25285531 Page: p.4, 6
28 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 28 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 28 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/20538761 Page: p.5,15	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/20538761 Page: p.5,15	DLT: Dizziness, Coordination abnormal... Dose limiting toxicities: Dizziness (16.7%) Coordination abnormal (grade 3, 33.3%) Tonic clonic movements (grade 3, 16.7%) Somnolence (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/20538761 Page: p.5,15
7 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 7 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 7 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/20538761 Page: p.5,15	unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/20538761 Page: p.5,15	DLT: Coordination abnormal... Dose limiting toxicities: Coordination abnormal (33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/20538761 Page: p.5,15

AEs

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY572578	https://www.001chemical.com/chem/803712-67-6
Ambinter	Amb22520492	http://www.ambinter.com/reference/22520492
BOC Sciences	803712-67-6	https://www.bocsci.com/obatoclax-cas-803712-67-6-item-91078.html
BioChemPartner	BCP20625	http://www.biochempartner.com/803712-67-6-BCP20625
Boerchem	BC203251	http://www.boerchem.com/?product_34136.html
Chem Scene	CS-0025474	http://www.chemscene.com/803712-67-6.html
ChemMol	44001449	http://www.chemmol.com/chemmol/44001449.html
Chemspace	CSSB00102513633	https://chem-space.com/CSSB00102513633
MedChem Express	HY-10969A	https://www.medchemexpress.com/obatoclax-1.html
Molcore	MC572578	https://www.molcore.com/product/803712-67-6
Smolecule	S864937	https://www.smolecule.com/products/s864937
Synblock Inc	SB16622	http://www.synblock.com/product/803712-67-6.html

PubMed

Title	Date	PubMed
Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis.	2007 Dec 4	18040043
Phase I dose finding studies of obatoclax (GX15-070), a small molecule pan-BCL-2 family antagonist, in patients with advanced solid tumors or lymphoma.	2010 Aug 1	20538761
Obatoclax mesylate : pharmacology and potential for therapy of hematological neoplasms.	2012 Mar	22324354

Patents

Sample Use Guides

In Vivo Use Guide

30 mg by vein over 3 hours Days 1-3, 14-day cycle

Route of Administration: Intravenous

In Vitro Use Guide

Obatoclax completely inhibits Bak recovery of Mcl-1 at 5 uM in SK-Mel5 cells and overcomes resistance to ABT-373-induced apoptosis conferred by Mcl-1 in KB/Bcl-2 cells.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:36:40 GMT 2023` Edited by `admin` on `Fri Dec 15 16:36:40 GMT 2023`
Record UNII	QN4128B52A
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

OBATOCLAX

Official Name

English

1H-INDOLE, 2-(2-((3,5-DIMETHYL-1H-PYRROL-2-YL)METHYLENE)-3-METHOXY-2H-PYRROL-5-YL)-

Systematic Name

English

Obatoclax [WHO-DD]

Common Name

English

obatoclax [INN]

Common Name

English

GX15-070

Code

English

2-(2-((3,5-DIMETHYL-1H-PYRROL-2-YL)METHYLENE)-3-METHOXY-2H-PYRROL-5-YL)-1H-INDOLE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C274