Synonym
VCC234718; VCC-234718; VCC 234718.
IUPAC/Chemical Name
Cyclohexyl[4-(5-isoquinolinylsulfonyl)-1-piperazinyl]methanone
InChi Key
RQGSIJUNMAAIRB-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H25N3O3S/c24-20(16-5-2-1-3-6-16)22-11-13-23(14-12-22)27(25,26)19-8-4-7-17-15-21-10-9-18(17)19/h4,7-10,15-16H,1-3,5-6,11-14H2
SMILES Code
O=C(C1CCCCC1)N2CCN(S(=O)(C3=CC=CC4=C3C=CN=C4)=O)CC2
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
More Info
This compound binds at the NAD+ site, after IMP has bound, and makes direct interactions with IMP; therefore, the inhibitor is by definition uncompetitive. VCC234718 forms strong pi interactions with the Y487 residue side chain from the adjacent protomer in the tetramer, explaining the resistance-conferring mutation. In addition to sensitizing Mtb to VCC234718, depletion of GuaB2 was bactericidal in Mtb in vitro and in macrophages. When supplied at a high concentration (≥125 μM), guanine alleviated the toxicity of VCC234718 treatment or GuaB2 depletion via purine salvage. However, transcriptional silencing of guaB2 prevented Mtb from establishing an infection in mice, confirming that Mtb has limited access to guanine in this animal model. Together, these data provide compelling validation of GuaB2 as a new tuberculosis drug target.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
387.50
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 |
1: Shapiro AB, Gao N, Jahić H, Carter NM, Chen A, Miller AA. Reversibility of
Covalent, Broad-Spectrum Serine β-Lactamase Inhibition by the
Diazabicyclooctenone ETX2514. ACS Infect Dis. 2017 Nov 10;3(11):833-844. doi:
10.1021/acsinfecdis.7b00113. Epub 2017 Aug 28. PubMed PMID: 28835096.
2: Singh V, Donini S, Pacitto A, Sala C, Hartkoorn RC, Dhar N, Keri G, Ascher DB,
Mondésert G, Vocat A, Lupien A, Sommer R, Vermet H, Lagrange S, Buechler J,
Warner DF, McKinney JD, Pato J, Cole ST, Blundell TL, Rizzi M, Mizrahi V. The
Inosine Monophosphate Dehydrogenase, GuaB2, Is a Vulnerable New Bactericidal Drug
Target for Tuberculosis. ACS Infect Dis. 2017 Jan 13;3(1):5-17. doi:
10.1021/acsinfecdis.6b00102. Epub 2016 Sep 8. PubMed PMID: 27726334; PubMed
Central PMCID: PMC5241705.
