Synonym
R-10015; R 10015; R10015;
IUPAC/Chemical Name
Methyl 2-(1-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl) piperidin-4-yl)-1H-benzo[d]imidazole-5-carboxylate
InChi Key
MGRJCGXCUUCOQG-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H19ClN6O2/c1-29-20(28)12-2-3-14-15(8-12)26-17(25-14)11-4-6-27(7-5-11)19-16-13(21)9-22-18(16)23-10-24-19/h2-3,8-11H,4-7H2,1H3,(H,25,26)(H,22,23,24)
SMILES Code
O=C(C1=CC=C2NC(C3CCN(C4=C5C(NC=C5Cl)=NC=N4)CC3)=NC2=C1)OC
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
A dynamic actin cytoskeleton is necessary for viral entry, intracellular migration, and virion release. For HIV-1 infection, during entry, the virus triggers early actin activity by hijacking chemokine coreceptor signaling, which activates a host dependency factor, cofilin, and its kinase, the LIM domain kinase (LIMK). Although knockdown of human LIM domain kinase 1 (LIMK1) with short hairpin RNA (shRNA) inhibits HIV infection, no specific small-molecule inhibitor of LIMK has been available. Here, we describe the design and discovery of novel classes of small-molecule inhibitors of LIMK for inhibiting HIV infection
Biological target:
R-10015 acts as a potent and selective inhibitor of LIMK and binds to the ATP-binding pocket, with an IC50 of 38 nM for human LIMK1.
In vitro activity:
This study identified R10015 as a lead compound that blocks LIMK activity by binding to the ATP-binding pocket. R10015 specifically blocks viral DNA synthesis, nuclear migration, and virion release. R10015 inhibits multiple viruses, including Zaire ebolavirus, Rift Valley fever virus, Venezuelan equine encephalitis virus, and herpes simplex virus 1, suggesting that LIMK inhibitors could be developed as a new class of broad-spectrum antiviral drugs.
Reference: J Virol. 2017 Jun 9;91(13):e02418-16. https://pubmed.ncbi.nlm.nih.gov/28381571/
In vivo activity:
Treatment of resting CD4+ T cells with R10015 blocked cofilin phosphorylation and abrogated IP-10-mediated enhancement of HIV latent infection. Therapeutic targeting of IP-10 may be a potential strategy for inhibiting HIV latent infection.
Reference: Front Immunol. 2021 Aug 10;12:656663. https://pubmed.ncbi.nlm.nih.gov/34447368/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
3.2 |
10.00 |
|
| DMSO |
3.2 |
10.00 |
|
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
410.86
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. Yi F, Guo J, Dabbagh D, Spear M, He S, Kehn-Hall K, Fontenot J, Yin Y, Bibian M, Park CM, Zheng K, Park HJ, Soloveva V, Gharaibeh D, Retterer C, Zamani R, Pitt ML, Naughton J, Jiang Y, Shang H, Hakami RM, Ling B, Young JAT, Bavari S, Xu X, Feng Y, Wu Y. Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol. 2017 Jun 9;91(13):e02418-16. doi: 10.1128/JVI.02418-16. PMID: 28381571; PMCID: PMC5469273.
2. Wang Z, Yin X, Ma M, Ge H, Lang B, Sun H, He S, Fu Y, Sun Y, Yu X, Zhang Z, Cui H, Han X, Xu J, Ding H, Chu Z, Shang H, Wu Y, Jiang Y. IP-10 Promotes Latent HIV Infection in Resting Memory CD4+ T Cells via LIMK-Cofilin Pathway. Front Immunol. 2021 Aug 10;12:656663. doi: 10.3389/fimmu.2021.656663. PMID: 34447368; PMCID: PMC8383741.
In vitro protocol:
1. Yi F, Guo J, Dabbagh D, Spear M, He S, Kehn-Hall K, Fontenot J, Yin Y, Bibian M, Park CM, Zheng K, Park HJ, Soloveva V, Gharaibeh D, Retterer C, Zamani R, Pitt ML, Naughton J, Jiang Y, Shang H, Hakami RM, Ling B, Young JAT, Bavari S, Xu X, Feng Y, Wu Y. Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol. 2017 Jun 9;91(13):e02418-16. doi: 10.1128/JVI.02418-16. PMID: 28381571; PMCID: PMC5469273.
In vivo protocol:
1. Wang Z, Yin X, Ma M, Ge H, Lang B, Sun H, He S, Fu Y, Sun Y, Yu X, Zhang Z, Cui H, Han X, Xu J, Ding H, Chu Z, Shang H, Wu Y, Jiang Y. IP-10 Promotes Latent HIV Infection in Resting Memory CD4+ T Cells via LIMK-Cofilin Pathway. Front Immunol. 2021 Aug 10;12:656663. doi: 10.3389/fimmu.2021.656663. PMID: 34447368; PMCID: PMC8383741.
Yi F, Guo J, Dabbagh D, Spear M, He S, Kehn-Hall K, Fontenot J, Yin Y, Bibian M, Park CM, Zheng K, Park HJ, Soloveva V, Gharaibeh D, Retterer C, Zamani R, Pitt ML, Naughton J, Jiang Y, Shang H, Hakami RM, Ling B, Young JAT, Bavari S, Xu X, Feng Y, Wu Y. Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol. 2017 Jun 9;91(13):e02418-16. doi: 10.1128/JVI.02418-16. PMID: 28381571; PMCID: PMC5469273.
Wang Z, Yin X, Ma M, Ge H, Lang B, Sun H, He S, Fu Y, Sun Y, Yu X, Zhang Z, Cui H, Han X, Xu J, Ding H, Chu Z, Shang H, Wu Y, Jiang Y. IP-10 Promotes Latent HIV Infection in Resting Memory CD4+ T Cells via LIMK-Cofilin Pathway. Front Immunol. 2021 Aug 10;12:656663. doi: 10.3389/fimmu.2021.656663. PMID: 34447368; PMCID: PMC8383741.
