Synonym
NVS-PAK1-1; NVSPAK11; NVS PAK1 1;
IUPAC/Chemical Name
3(S)-[2-Chloro-5-(2,2-difluoro-ethyl)-8-fluoro-5H-dibenzo[b,e][1,4]diazepin-11-ylamino]-pyrrolidine-1-carboxylic acid isopropylamide
InChi Key
OINGHOPGNMYCAB-INIZCTEOSA-N
InChi Code
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
SMILES Code
O=C(N1C[C@@H](NC2=NC3=CC(F)=CC=C3N(CC(F)F)C4=CC=C(Cl)C=C42)CC1)NC(C)C
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
NVS-PAK1-1 is a potent and selective allosteric PAK1 inhibitor with an IC50 of 5 nM.
In vitro activity:
NVS-PAK1-1 is almost 100× more selective for PAK1 than PAK2 and demonstrated excellent PAK1 inhibition in vitro. NVS-PAK1-1 potently inhibited PAK1 autophosphorylation in MS02 cells (Fig. 4A) and reduced the proliferation of MS02 and HEI-193 cells with an IC50 of 4.7 and 6.2 μM, respectively (Fig. 4B and C).
Reference: Hum Mol Genet. 2021 Aug 12;30(17):1607-1617. https://pubmed.ncbi.nlm.nih.gov/34075397/
In vivo activity:
After 3 months of treatment, mice which received NVS-PAK1-1 did not exhibit a significant reduction in sensorineural hearing loss (Fig. 4G) but did have a modest, but statistically significant, reduction in average DRG volume compared with mice treated with 1-ABT alone or the vehicle control (Fig. 4H).
Reference: Hum Mol Genet. 2021 Aug 12;30(17):1607-1617. https://pubmed.ncbi.nlm.nih.gov/34075397/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
0.0 |
104.18 |
| DMF:PBS (pH 7.2) (1:1) |
0.5 |
1.04 |
| DMSO |
79.8 |
166.16 |
| Ethanol |
58.0 |
120.85 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
479.93
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
Hawley E, Gehlhausen J, Karchugina S, Chow HY, Araiza-Olivera D, Radu M, Smith A, Burks C, Jiang L, Li X, Bessler W, Masters A, Edwards D, Burgin C, Jones D, Yates C, Clapp DW, Chernoff J, Park SJ. PAK1 inhibition reduces tumor size and extends the lifespan of mice in a genetically engineered mouse model of Neurofibromatosis Type 2 (NF2). Hum Mol Genet. 2021 Aug 12;30(17):1607-1617. doi: 10.1093/hmg/ddab106. PMID: 34075397; PMCID: PMC8369838.
In vitro protocol:
Hawley E, Gehlhausen J, Karchugina S, Chow HY, Araiza-Olivera D, Radu M, Smith A, Burks C, Jiang L, Li X, Bessler W, Masters A, Edwards D, Burgin C, Jones D, Yates C, Clapp DW, Chernoff J, Park SJ. PAK1 inhibition reduces tumor size and extends the lifespan of mice in a genetically engineered mouse model of Neurofibromatosis Type 2 (NF2). Hum Mol Genet. 2021 Aug 12;30(17):1607-1617. doi: 10.1093/hmg/ddab106. PMID: 34075397; PMCID: PMC8369838.
In vivo protocol:
Hawley E, Gehlhausen J, Karchugina S, Chow HY, Araiza-Olivera D, Radu M, Smith A, Burks C, Jiang L, Li X, Bessler W, Masters A, Edwards D, Burgin C, Jones D, Yates C, Clapp DW, Chernoff J, Park SJ. PAK1 inhibition reduces tumor size and extends the lifespan of mice in a genetically engineered mouse model of Neurofibromatosis Type 2 (NF2). Hum Mol Genet. 2021 Aug 12;30(17):1607-1617. doi: 10.1093/hmg/ddab106. PMID: 34075397; PMCID: PMC8369838.
1: Karpov AS, Amiri P, Bellamacina C, Bellance MH, Breitenstein W, Daniel D, Denay R, Fabbro D, Fernandez C, Galuba I, Guerro-Lagasse S, Gutmann S, Hinh L, Jahnke W, Klopp J, Lai A, Lindvall MK, Ma S, Mobitz H, Pecchi S, Rummel G, Shoemaker K, Trappe J, Voliva C, Cowan-Jacob SW, Marzinzik AL. Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor. ACS medicinal chemistry letters. 2015;6:776-81.
