Synonym
GSK3145095; GSK-3145095; GSK 3145095;
IUPAC/Chemical Name
(S)-5-benzyl-N-(7,9-difluoro-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl)-4H-1,2,4-triazole-3-carboxamide
InChi Key
ATQAGKAMBISZQM-HNNXBMFYSA-N
InChi Code
InChI=1S/C20H17F2N5O2/c21-13-9-12-6-7-15(19(28)25-17(12)14(22)10-13)23-20(29)18-24-16(26-27-18)8-11-4-2-1-3-5-11/h1-5,9-10,15H,6-8H2,(H,23,29)(H,25,28)(H,24,26,27)/t15-/m0/s1
SMILES Code
O=C(C1=NN=C(CC2=CC=CC=C2)N1)N[C@H]3CCC4=CC(F)=CC(F)=C4NC3=O
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
>3 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
More Info
RIPK1, a serine-threonine kinase that normally plays a key role in inflammation and cell death in response to tissue damage and pathogen recognition, is overexpressed in certain cancer types and may be associated with oncogenesis and promotion of the immunosuppressive nature of the TME.
RIP1 regulates cell death and inflammation and is believed to play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases and cancer. While small-molecule inhibitors of RIP1 kinase have been advanced to the clinic for inflammatory diseases and CNS indications, RIP1 inhibitors for oncology indications have yet to be described.
Biological target:
GSK3145095 is a RIP1 kinase inhibitor with an IC50 of 6.3 nM.
In vitro activity:
Compound 6 (GSK3145095) potently binds to RIP1 with exquisite kinase specificity and has excellent activity in blocking RIP1 kinase-dependent cellular responses.
Reference: ACS Med Chem Lett. 2019 May 9;10(6):857-862. https://pubmed.ncbi.nlm.nih.gov/31223438/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
164.5 |
413.96 |
| Ethanol |
6.0 |
15.10 |
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
397.39
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:
1. Harris PA, Marinis JM, Lich JD, Berger SB, Chirala A, Cox JA, Eidam PM, Finger JN, Gough PJ, Jeong JU, Kang J, Kasparcova V, Leister LK, Mahajan MK, Miller G, Nagilla R, Ouellette MT, Reilly MA, Rendina AR, Rivera EJ, Sun HH, Thorpe JH, Totoritis RD, Wang W, Wu D, Zhang D, Bertin J, Marquis RW. Identification of a RIP1 Kinase Inhibitor Clinical Candidate (GSK3145095) for the Treatment of Pancreatic Cancer. ACS Med Chem Lett. 2019 May 9;10(6):857-862. doi: 10.1021/acsmedchemlett.9b00108. PMID: 31223438; PMCID: PMC6580371.
In vitro protocol:
1. Harris PA, Marinis JM, Lich JD, Berger SB, Chirala A, Cox JA, Eidam PM, Finger JN, Gough PJ, Jeong JU, Kang J, Kasparcova V, Leister LK, Mahajan MK, Miller G, Nagilla R, Ouellette MT, Reilly MA, Rendina AR, Rivera EJ, Sun HH, Thorpe JH, Totoritis RD, Wang W, Wu D, Zhang D, Bertin J, Marquis RW. Identification of a RIP1 Kinase Inhibitor Clinical Candidate (GSK3145095) for the Treatment of Pancreatic Cancer. ACS Med Chem Lett. 2019 May 9;10(6):857-862. doi: 10.1021/acsmedchemlett.9b00108. PMID: 31223438; PMCID: PMC6580371.
Identification of a RIP1 Kinase Inhibitor Clinical Candidate (GSK3145095) for the Treatment of Pancreatic Cancer
Philip A. Harris, Jill M. Marinis, John D. Lich, Scott B. Berger, Anirudh Chirala, Julie A. Cox, Patrick M. Eidam, Joshua N. Finger, Peter J. Gough, Jae U. Jeong, James Kang, Viera Kasparcova, Lara K. Leister, Mukesh K. Mahajan, George Miller, Rakesh Nagilla, Michael T. Ouellette, Michael A. Reilly, Alan R. Rendina, Elizabeth J. Rivera, Helen H. Sun, James H. Thorpe, Rachel D. Totoritis, Wei Wang, Dongling Wu, Daohua Zhang, John Bertin, and Robert W. Marquis
Publication Date (Web): May 9, 2019 (Featured Letter)
DOI: 10.1021/acsmedchemlett.9b00108
