NVS-PAK1-1

• CAT Number: I011863
• CAS Number: 1783816-74-9
• Molecular Formula: C23H25ClF3N5O
• Molecular Weight: 479.93
• Purity: ≥95%
• Synonyms: NVS-PAK1-1; NVSPAK11; NVS PAK1 1
• Target: Cytoskeleton
• Storage: RT
• InChI: InChI=1S/C23H25ClF3N5O/c1-13(2)28-23(33)31-8-7-16(11-31)29-22-17-9-14(24)3-5-19(17)32(12-21(26)27)20-6-4-15(25)10-18(20)30-22/h3-6,9-10,13,16,21H,7-8,11-12H2,1-2H3,(H,28,33)(H,29,30)/t16-/m0/s1
• InChIKey: OINGHOPGNMYCAB-INIZCTEOSA-N
• SMILES: O=C(N1C[C@@H](NC2=NC3=CC(F)=CC=C3N(CC(F)F)C4=CC=C(Cl)C=C42)CC1)NC(C)C

NVS-PAK1-1(CAT: I011863) is a small molecule inhibitor that specifically targets p21-activated kinase 1 (PAK1), a serine/threonine kinase that plays a key role in cell proliferation, migration, and survival. Overactivity of PAK1 has been implicated in various diseases including cancer, neurodegenerative disorders, and cardiovascular diseases. NVS-PAK1-1 has been shown to effectively inhibit PAK1 activity in both in vitro and in vivo studies, and is being investigated as a potential therapeutic agent for the treatment of PAK1-driven diseases. Preclinical studies have shown promising results, but further clinical trials are needed to determine its safety and efficacy in humans.

Reference

1. ACS Med Chem Lett. 2015 May 22;6(7):776-81. doi: 10.1021/acsmedchemlett.5b00102.
eCollection 2015 Jul 9.

Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1
Inhibitor.

Karpov AS(1), Amiri P(2), Bellamacina C(2), Bellance MH(1), Breitenstein W(1),
Daniel D(2), Denay R(1), Fabbro D(1), Fernandez C(1), Galuba I(1), Guerro-Lagasse
S(1), Gutmann S(1), Hinh L(2), Jahnke W(1), Klopp J(1), Lai A(2), Lindvall MK(2),
Ma S(2), Möbitz H(1), Pecchi S(2), Rummel G(1), Shoemaker K(2), Trappe J(1),
Voliva C(2), Cowan-Jacob SW(1), Marzinzik AL(1).

Author information:
(1)Novartis Institutes for BioMedical Research , Novartis Campus, CH-4056 Basel,
Switzerland.
(2)Novartis Institutes for BioMedical Research , 5300 Chiron Way, Emeryville,
California 94608, United States.

The discovery of inhibitors targeting novel allosteric kinase sites is very
challenging. Such compounds, however, once identified could offer exquisite
levels of selectivity across the kinome. Herein we report our structure-based
optimization strategy of a dibenzodiazepine hit 1, discovered in a fragment-based
screen, yielding highly potent and selective inhibitors of PAK1 such as 2 and 3.
Compound 2 was cocrystallized with PAK1 to confirm binding to an allosteric site
and to reveal novel key interactions. Compound 3 modulated PAK1 at the cellular
level and due to its selectivity enabled valuable research to interrogate
biological functions of the PAK1 kinase.