1432913-36-4 Usage
Biological Activity
gx-674 is an aryl sulfonamide class of antagonists that inhibits nav1.7 [1]nav (voltage-gated sodium) channels conduct ionic currents that initiate action potentials in neurons and muscles cells. human express 9 nav channel isoforms (nav 1.1-1.9), among which nav 1.7 channel are express in olfactory epithelium, sympathetic ganglion, and dorsal root ganglion sensory neurons. gain-of-function mutations in nav1.7 are associated with extreme pain disorders whereas loss-of-function mutations cause congenital insensitivity to pain in individuals. [1]in hek293 cells, patch clamp analysis was perform for human nav channels. gx-674 shows potent inhibition effect on nav.1.7 (ic50= 0.1nm). gx-674 also exhibits substantial selectivity on different nav subtypes. it shows much higher inhibitory effects on nav 1.7 over other nav isoform, such as 100000 times more potent for nav1.7 than for nav 1.5. gx-74 is also reported to bind to a high-affinity, isoform-selective, and extracellularly accessible site on vsd4. (i.e. one of the peripheral voltage-sensor domains of nav.1.7). [1]
references
1. ahuja s, mukund s, deng l et al. structural basis of nav1.7 inhibition by an isoform-selective small-molecule antagonist. science. 2015 dec 18;350(6267):aac5464.
Check Digit Verification of cas no
The CAS Registry Mumber 1432913-36-4 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,3,2,9,1 and 3 respectively; the second part has 2 digits, 3 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 1432913-36:
(9*1)+(8*4)+(7*3)+(6*2)+(5*9)+(4*1)+(3*3)+(2*3)+(1*6)=144
144 % 10 = 4
So 1432913-36-4 is a valid CAS Registry Number.
1432913-36-4Relevant academic research and scientific papers
Discovery of Aryl Sulfonamides as Isoform-Selective Inhibitors of NaV1.7 with Efficacy in Rodent Pain Models
Focken, Thilo,Liu, Shifeng,Chahal, Navjot,Dauphinais, Maxim,Grimwood, Michael E.,Chowdhury, Sultan,Hemeon, Ivan,Bichler, Paul,Bogucki, David,Waldbrook, Matthew,Bankar, Girish,Sojo, Luis E.,Young, Clint,Lin, Sophia,Shuart, Noah,Kwan, Rainbow,Pang, Jodie,Chang, Jae H.,Safina, Brian S.,Sutherlin, Daniel P.,Johnson,Dehnhardt, Christoph M.,Mansour, Tarek S.,Oballa, Renata M.,Cohen, Charles J.,Robinette, C. Lee
, p. 277 - 282 (2016/03/22)
We report on a novel series of aryl sulfonamides that act as nanomolar potent, isoform-selective inhibitors of the human sodium channel hNaV1.7. The optimization of these inhibitors is described. We aimed to improve potency against hNaV1.7 while minimizing off-target safety concerns and generated compound 3. This agent displayed significant analgesic effects in rodent models of acute and inflammatory pain and demonstrated that binding to the voltage sensor domain 4 site of NaV1.7 leads to an analgesic effect in vivo. Our findings corroborate the importance of hNaV1.7 as a drug target for the treatment of pain.
