BATABULIN SODIUM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H6F6NO3S.Na
Molecular Weight	393.237
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].COC1=C(F)C=C([N-]S(=O)(=O)C2=C(F)C(F)=C(F)C(F)=C2F)C=C1

InChI

InChIKey=UWPXRVDIKGZQQW-UHFFFAOYSA-N

InChI=1S/C13H6F6NO3S.Na/c1-23-7-3-2-5(4-6(7)14)20-24(21,22)13-11(18)9(16)8(15)10(17)12(13)19;/h2-4H,1H3;/q-1;+1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10318945 | https://www.ncbi.nlm.nih.gov/pubmed/18279576 | https://www.ncbi.nlm.nih.gov/pubmed/15831236 | http://adisinsight.springer.com/drugs/800010660

Batabulin or T138067 (2-fluoro-1-methoxy-4-pentafluorophenylsulfonamidobenzene) covalently and selectively modifies the beta1, beta2, and beta4 isotypes of beta-tubulin at a conserved cysteine residue, thereby disrupting microtubule polymerization. Cells exposed to batabulin become altered in shape, indicating a collapse of the cytoskeleton, and show an increase in chromosomal ploidy. Batabulin is equally efficacious in inhibiting the growth of sensitive and multidrug-resistant human tumor xenografts in athymic nude mice. Batabulin has been in clinical trials for the treatment of cancers (breast cancer, colorectal cancer, glioma, hepatocellular carcinoma, non-small cell lung cancer). It does not have clinical activity in the treatment of colorectal cancer and glioma. Batabulin development was discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tubulin beta chain 8 Target ID: P07437 Gene ID: 203068.0 Gene Symbol: TUBB Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10318945	Binding Agent 1064		2.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Hepatocellular carcinoma 83 Sources: https://clinicaltrials.gov/ct2/show/NCT00057382	Primary	Phase III 656	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://clinicaltrials.gov/ct2/show/NCT00022243	Primary	Phase II 1132	Unknown Approved Use Unknown
Advanced refractory cancer 2 Sources: https://clinicaltrials.gov/ct2/show/NCT00003359	Primary	Phase I 428	Unknown Approved Use Unknown
Glioma 21 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15831236	Primary	Phase II 1132	Unknown Approved Use Unknown
Colorectal cancer 101 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18279576	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
4046 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831236	330 mg/m² 1 times / week multiple, intravenous dose: 330 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		BREQUINAR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
9653.7 mg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831236	330 mg/m² 1 times / week multiple, intravenous dose: 330 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		BREQUINAR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831236	330 mg/m² 1 times / week multiple, intravenous dose: 330 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		BREQUINAR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
330 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 330 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 330 mg/m2, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/jco.2004.22.90140.4087	unhealthy, ADULT n = 2 Health Status: unhealthy Condition: hepatocellular carcinoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://ascopubs.org/doi/abs/10.1200/jco.2004.22.90140.4087	DLT: Thrombocytopenia... Dose limiting toxicities: Thrombocytopenia (grade 1, 100%) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2004.22.90140.4087
330 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 330 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 330 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/15831236 Page: p.185	unhealthy, ADULT n = 18 Health Status: unhealthy Condition: malignant glioma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/15831236 Page: p.185	Sources: https://pubmed.ncbi.nlm.nih.gov/15831236 Page: p.185
300 mg/m2 1 times / week multiple, intravenous MTD Dose: 300 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 300 mg/m2, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/jco.2004.22.90140.4087	unhealthy, ADULT n = 7 Health Status: unhealthy Condition: hepatocellular carcinoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: https://ascopubs.org/doi/abs/10.1200/jco.2004.22.90140.4087	DLT: Neutropenia... Dose limiting toxicities: Neutropenia (grade 3, 42.9%) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2004.22.90140.4087

AEs

AE	Significance	Dose	Population
Thrombocytopenia	grade 1, 100% DLT	330 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 330 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 330 mg/m2, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/jco.2004.22.90140.4087	unhealthy, ADULT n = 2 Health Status: unhealthy Condition: hepatocellular carcinoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://ascopubs.org/doi/abs/10.1200/jco.2004.22.90140.4087
Neutropenia	grade 3, 42.9% DLT	300 mg/m2 1 times / week multiple, intravenous MTD Dose: 300 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 300 mg/m2, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/jco.2004.22.90140.4087	unhealthy, ADULT n = 7 Health Status: unhealthy Condition: hepatocellular carcinoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: https://ascopubs.org/doi/abs/10.1200/jco.2004.22.90140.4087

Sourcing

Vendor/Aggregator	ID	URL
Chem Scene	CS-0007170	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0007170
Chem Scene	CS-0132209	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0132209
Compound Cloud	216324
Compound Cloud	23669770
Enamine	Z1478321775	https://www.enaminestore.com/blog/real/Z1478321775/
MedChem Express	HY-13563	https://www.medchemexpress.com/search.html?q=HY-13563A&ft=&fa=&fp=
MedChem Express	HY-13563A	https://www.medchemexpress.com/search.html?q=HY-13563A&ft=&fa=&fp=
MuseChem	I003955	https://www.musechem.com/product/I003955.html
mcule	MCULE-8874760030	https://mcule.com/MCULE-8874760030/

PubMed

Title	Date	PubMed
Selective, covalent modification of beta-tubulin residue Cys-239 by T138067, an antitumor agent with in vivo efficacy against multidrug-resistant tumors.	1999 May 11	10318945
Hydrophilic, pro-drug analogues of T138067 are efficacious in controlling tumor growth in vivo and show a decreased ability to cross the blood brain barrier.	2001 Oct 25	11606124
Phase 2 study of T138067-sodium in patients with malignant glioma: Trial of the National Cancer Institute of Canada Clinical Trials Group.	2005 Apr	15831236

Patents

Sample Use Guides

In Vivo Use Guide

In clinical trials, patients with recurrent anaplastic astrocytoma or glioblastoma multiforme were treated intravenously with 330 mg/m^2 of batabulin (T138067-sodium) weekly. Treatment was continued until the patient experienced either unacceptable toxicity or progressive disease.

Route of Administration: Intravenous

In Vitro Use Guide

The effects of batabulin (T138067) on the cytoskeleton and morphology of MCF7 cells were investigated. In the absence of batabulin, cells showed the typical morphology of adherent growing cells. However, in the presence of 100 nM batabulin for 9 hr, approximately 40% of the cells adopted a rounded morphology and became detached from the plate surface. At slightly higher drug concentrations (300 nM), almost all cells showed these morphological changes.

Name

Type

Language

BATABULIN SODIUM

Official Name

English

BATABULIN SODIUM [USAN]

Common Name

English

BENZENESULFONAMIDE, 2,3,4,5,6-PENTAFLUORO-N-(3-FLUORO-4-METHOXYPHENYL)-, SODIUM SALT

Common Name

English

2-FLUORO-1-METHOXY-4-PENTAFLUOROPHENYLSULFONAMIDOBENZENE, SODIUM SALT

Common Name

English

Sodium 2,3,4,5,6-pentafluoro-N-(3-fluoro-4-methoxyphenyl)benzenesulfonamidate

Systematic Name

English

T-138067 SODIUM

Code

English

T138067-SODIUM

Code

English

Batabulin sodium [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67421