HG-7-85-01

SKU: orb1691859

Description

HG-7-85-01 is a potent ATP-competitive, type II inhibitor targeting BCR-ABL (including T315I mutant), PDGFRα, Kit, and Src kinases. It demonstrates robust anti-proliferative activity in vitro, inducing cell cycle arrest and apoptosis in leukemia cell lines, and has shown efficacy in preclinical in vivo models of BCR-ABL-driven cancers.

Research Area

Cardiovascular Research, Cell Biology, Epigenetics & Chromatin, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1258391-13-7
• MW: 608.68
• Purity: 98.08% (May vary between batches)
• Formula: C₃₁H₃₁F₃N₆O₂S
• SMILES: O=C(NC1=CC=C(C(=C1)C(F)(F)F)CN2CCN(CC)CC2)C3=CC=CC(=C3)C4=NC=5SC(=NC5C=C4)NC(=O)C6CC6
• Target: Bcr-Abl,Src,c-Kit,PDGFR,JAK,Apoptosis
• Solubility: DMSO:100 mg/mL (164.29 mM)

Bioactivity

• Target IC50:
  JAK1:120 nM|PDGFRα:440 nM|KDR:20 nM|MK5:560 nM|RET:30 nM|BCR-ABL (T315I):3 nM
• In Vivo:
  HG-7-85-01 has limited oral bioavailability (BAV % F mouse = 5 %, rat = 19 %), a moderate half life (T 1/2 mouse =1.1 h rat = 5.8 hours), a relative low maximal serum concentration (C max mouse = 106 ng/mL at 10 mg/kg , rat = 292 ng/mL and 2 mg/kg ) and a relatively high clearance (Cl mouse = 23 ml/min/kg, rat = 13 ml/min/kg) .
• In Vitro:
  HG-7-85-01 (0-1 μM; 24 hours; BCR-ABL-, BCR-ABL-T315I-, Kit-T670I-, PDGFRα-T674M-, and PDGFRα-T674I-expressing cells) treatment leads to G0G1 arrest of BCR-ABL-expressing cells . HG-7-85-01 (0-1 μM; 72 hours; BCR-ABL-, BCR-ABL-T315I-, Kit-T670I-, PDGFRα-T674M-, and PDGFRα-T674I-expressing cells) treatment also leads to induction of apoptosis of BCR-ABL-expressing cells . HG-7-85-01 treatment potently and selectively inhibits the proliferation of 32D- and Ba/F3 cells expressing nonmutant BCR-ABL and the BCR-ABL-T315I gatekeeper mutant. HG-7-85-01 shows higher potency against nonmutant BCR-ABL and BCR-ABL-T315I (IC 50 = 0.06-0.14 μM) . HG-7-85-01 inhibits BCR-ABL kinase activity in a concentration-dependent manner, suggesting selective targeting of the BCR-ABL kinase as the mechanism of action of HG-7-85-01 . HG-7-85-01 potently inhibits the proliferation of Ba/F3 cells expressing the Kit-T670I gatekeeper mutation (Ba/F3- Kit-T670I) and Ba/F3 cells expressing TEL/PDGFRβ and no effect on parental Ba/F3 cells. HG-7-85-01 inhibits Kit, PDGFR phosphorylation in a concentration-dependent manner . The PDGFRα-T674M and PDGFRα-T674I gatekeeper mutant variants are highly responsive to HG-7-85-01 and significant IL-3 rescue . HG-7-85-01 inhibits the proliferation of Ba/F3 cells transformed with human c-Src (EC 50 = 190 nM), T338I Src (EC 50 = 290 nM), and T338M Src (EC 50 = 150 nM; chicken c-Src numbering). And potently inhibits the proliferation of exon 11 Kit mutant-expressing cells, exon 9 kit mutant-expressing cells are significantly less responsive . Cell Cycle Analysis Cell Line: BCR-ABL-, BCR-ABL-T315I-, Kit-T670I-, PDGFRα-T674M-, and PDGFRα-T674I-expressing cells Concentration: 0 μM, 0.01 μM, 0.1 μM and 1 μM Incubation Time: 24 hours Result: Led to G0G1 arrest of BCR-ABL-expressing cells. Apoptosis Analysis Cell Line: BCR-ABL-, BCR-ABL-T315I-, Kit-T670I-, PDGFRα-T674M-, and PDGFRα-T674I-expressing cells Concentration: 0 μM, 0.01 μM, 0.1 μM and 1 μM Incubation Time: 72 hours Result: Led to induction of apoptosis of BCR-ABL-expressing cells.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

HG78501, HG-7-85-01, HG 7 85 01

Compound Identifiers

PubChem CID

51359962