803712-67-6

Basic information

• Product Name: obatoclax
• Synonyms: obatoclax;1H-Indole, 2-[2-[(3,5-diMethyl-1H-pyrrol-2-yl)Methylene]-3-Methoxy-2H-pyrrol-5-yl]-;2-[2-[(3,5-Dimethyl-1H-pyrrol-2-yl)methylene]-3-methoxy-2H-pyrrol-5-yl]-1H-indole
• CAS NO: 803712-67-6
• Molecular Formula: C20H19N3O
• Molecular Weight: 317.38
• Mol File: 803712-67-6.mol
• Article Data: 6

Chemical Properties

• Appearance: /
• CAS DataBase Reference: obatoclax(CAS DataBase Reference)
• NIST Chemistry Reference: obatoclax(803712-67-6)
• EPA Substance Registry System: obatoclax(803712-67-6)

Safety Data

• Hazardous Substances Data: 803712-67-6(Hazardous Substances Data)

Usage

Uses

Obatoclax is a small molecule mimetic of the BH3 domain of BCL-2 family proteins.

Enzyme inhibitor

This cell-permeable antiapoptotic agent (FWfree-base = 317.39 g/mol; FWmesylate-salt = 413.49 g/mol; CAS 803712-79-0; Solubility: 83 mg/mL DMSO, also known as GX15-070 and (Z)-2-(5-((3,5-dimethyl-1H-pyrrol-2- yl)methylene)-4-methoxy-5H-pyrrol-2-yl)-1H-indole mesylate, is a pan- Bcl-2 antagonist (Ki = 0.22 μM), binding to the BH3-binding groove of the B-cell lymphoma-2 (i.e., Bcl) family of proteins. Bcl-2 proteins confer a protective effect on malignant cells against death signals of apoptosis, and cancer cells that are resistant to various anti-cancer drugs and treatment regimen are often found to overexpress these Bcl-2, Bcl-XL, Mcl-1, Bcl-w, and A1/Bfl1. Obatoclax inhibits the binding of Bak to Mcl-1, up-regulating Bim, inducing cytochrome c release, and activating capase-3 in human myeloma cell lines. Acting as a single agent, it also induces potent cytotoxic responses against diverse patient-derived neoplasias, including multiple myeloma. Obatoclax retains its efficacy in cells overexpressing the P-glycoprotein multidrug-resistance transporter (P-gp), multidrug resistance-associated protein 2 (MRP2), or breast cancer resistance protein (BCRP) and might also act as a perpetrator drug in interactions with drugs, for example being substrates of CYP1A2 or BCRP. In human pharmacokinetic experiments, Obatoclax has Cmax of 10 to 80 ng/mL, below the level needed for effective in vitro activity against most tumor targets, a finding that is consistent with its failure to reach levels in a mouse xenograft tumor model sufficient to disrupt Mcl-1/Bax protein-protein interaction.

Upstream product

• 120-72-9 indole 
• 625-82-1 2,4-dimethyl-1H-pyrrole 
• 1001162-89-5 1-(N-methoxycarbonyl)indole-2-boronic acid 
• 1413942-20-7 C₁₀H₁₆N₂O₂ 
• 1107627-19-9 C₈H₇BBrNO₂ 
• 69778-83-2 4-methoxy-3-pyrrolin-2-one 
• 23999-91-9 1H-pyrrole-2,4-dicarboxaldehyde 
• 803712-71-2 N-((5-bromo-3-methoxy-2H-pyrrol-2-ylidene)-methyl)-N-ethylethanamine 
• 803712-70-1 tert-butyl 2-(5-formyl-4-methoxy-1H-pyrrol-2-yl)-1H-indole-1-carboxylate 

Relevant articles and documents

Synthesis and biological activity of obatoclax derivatives as novel and potent SHP-1 agonists

Obatoclax is a linear oligopyrrole compound which antagonizes the antiapoptotic effects of the Bcl-2 family. Herein we describe the synthesis of obatoclax derivatives by replacement of the pyrrole and indole ring of obatoclax with thiophene, furan and thiazolidinedione. The in vitro cytotoxicity of the newly synthesized compounds is evaluated against hepatocellular carcinoma cells. Pyrrole and indole substituents of obatoclax analogues exhibited potent inhibition of cell growth. Among the tested compounds, 5d and 5e were active at 6.3 and 13.2 μM against PLC5 cells. Further assays confirmed a correlation between cell death, and p-STAT3 inhibition and SHP-1 activation by these analogues.

A scalable process for the synthesis of the Bcl inhibitor obatoclax

Recently we created the novel indolylprodigiosin derivative 2 (obatodax) and demonstrated its ability to antagonize multiple members of the B-cell lymphoma (Bd) family of antiapoptotic proteins. The compound has shown potent anticancer activity in several animal tumor models. Obatodax is now in Phase 1b and 2 clinical trials directed against multiple hematologic and solid tumor malignancies. To support its clinical development, a new scalable synthesis was required. Obatodax has been prepared using a three-step synthesis, starting from commercially available 4-methoxy-3-pyrrolin-2-one. The reaction sequence involves a haloformylation reaction followed by a Suzuki cross-coupling reaction with an indole-2-boronic add. The synthesis is completed by an acid-mediated condensation with 2,4-dimethyl-1H-pyrrole.

Triheterocyclic compounds, compositions, and methods for treating cancer or viral diseases

The present invention relates to novel Triheterocyclic Compounds, compositions comprising a Triheterocyclic Compound, and methods useful for treating or preventing cancer or a neoplastic disorder comprising administering a Triheterocyclic Compound. The compounds, compositions, and methods of the invention are also useful for inhibiting the growth of a cancer cell or neoplastic cell, treating or preventing a viral infection, or inhibiting the replication and/or infectivity of a virus.