WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 522460
CAS#: 1235560-28-7
Description: ABT-639 is a potent and selective T-type calcium channel blocker. ABT-639 effectively reduces nociceptive and neuropathic pain in rats. ABT-639 produces robust antinociceptive activity in experimental pain models at doses that do not significantly alter psychomotor or hemodynamic function in the rat. ABT-639 was significantly less active at other Ca²⁺ channels (e.g. Ca(v)1.2 and Ca(v)2.2) (IC₅₀ > 30 μM). ABT-639 has high oral bioavailability (%F = 73), low protein binding (88.9%) and a low brain:plasma ratio (0.05:1) in rodents.
MedKoo Cat#: 522460
Name: ABT-639
CAS#: 1235560-28-7
Chemical Formula: C20H20ClF2N3O3S
Exact Mass: 455.0882
Molecular Weight: 455.9
Elemental Analysis: C, 52.69; H, 4.42; Cl, 7.78; F, 8.33; N, 9.22; O, 10.53; S, 7.03
Synonym: ABT-639; ABT 639; ABT639.
IUPAC/Chemical Name: (R)-4-chloro-2-fluoro-N-(2-fluorophenyl)-5-(octahydropyrrolo[1,2-a]pyrazine-2-carbonyl)benzenesulfonamide
InChi Key: AGPIHNZOZNKRGT-CYBMUJFWSA-N
InChi Code: InChI=1S/C20H20ClF2N3O3S/c21-15-11-17(23)19(30(28,29)24-18-6-2-1-5-16(18)22)10-14(15)20(27)26-9-8-25-7-3-4-13(25)12-26/h1-2,5-6,10-11,13,24H,3-4,7-9,12H2/t13-/m1/s1
SMILES Code: O=S(C1=CC(C(N2C[C@](CCC3)([H])N3CC2)=O)=C(Cl)C=C1F)(NC4=CC=CC=C4F)=O
Appearance: Solid powder
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, not in water
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: | ABT-639 is a novel, peripherally acting, selective T-type Ca2+ channel blocker. |
| In vitro activity: | At the same time, in order to verify whether the CACNA1H inhibitor ABT-639 has an inhibitory effect on H9c2 cells, this study used TUNEL staining (Figure 3A and 3B). The results showed that H9c2 cells had dramatically increased apoptosis after I/H treatment, and the apoptosis rate was markedly higher than the control group. After ABT-639 treated with H9c2 cells, it was found that the apoptosis rate was dramatically reduced. In addition, the results of immunofluorescence staining also found that ABT-639 can effectively inhibit the increase of CHOP into the nucleus induced by I/H treatment (Figure 3C and 3D). Reference: Eur Rev Med Pharmacol Sci. 2020 Dec;24(24):12887-12895. https://pubmed.ncbi.nlm.nih.gov/33378039/ |
| In vivo activity: | ABT-639 dose-dependently attenuates nociception in a capsaicin-induced secondary mechanical hyperalgesia model (Cap-SMH) (Figure 3). The antinociceptive activity of ABT-639 in this model is consistent with its dose-dependent antinociceptive activity in multiple models of neuropathic pain. Additionally, ABT-639 did not produce any decrement in balance or motor performance in the rat Edge test (ED50 > 300 mg/kg, or rat plasma 114 μg/mL, p.o.). Reference: ACS Med Chem Lett. 2015 Jun 11; 6(6): 641–644. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468402/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 9.71 | 21.3 | |
| DMF | 14.0 | 30.71 | |
| DMF:PBS (pH 7.2) (1:20) | 0.04 | 0.09 | |
| Ethanol | 0.5 | 1.1 |
The following data is based on the product molecular weight 455.9 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. Wang MX, Liu X, Li JM, Liu L, Lu W, Chen GC. Inhibition of CACNA1H can alleviate endoplasmic reticulum stress and reduce myocardial cell apoptosis caused by myocardial infarction. Eur Rev Med Pharmacol Sci. 2020 Dec;24(24):12887-12895. doi: 10.26355/eurrev_202012_24192. PMID: 33378039. 2. Hu J, Wu Q, Wang Z, Hong J, Chen R, Li B, Hu Z, Hu X, Zhang M. Inhibition of CACNA1H attenuates doxorubicin-induced acute cardiotoxicity by affecting endoplasmic reticulum stress. Biomed Pharmacother. 2019 Dec;120:109475. doi: 10.1016/j.biopha.2019.109475. Epub 2019 Sep 30. PMID: 31580970. 3. Zhang Q, Xia Z, Joshi S, Scott VE, Jarvis MF. Optimization of ADME Properties for Sulfonamides Leading to the Discovery of a T-Type Calcium Channel Blocker, ABT-639. ACS Med Chem Lett. 2015 Apr 28;6(6):641-4. doi: 10.1021/acsmedchemlett.5b00023. PMID: 26101566; PMCID: PMC4468402. 4. Jarvis MF, Scott VE, McGaraughty S, Chu KL, Xu J, Niforatos W, Milicic I, Joshi S, Zhang Q, Xia Z. A peripherally acting, selective T-type calcium channel blocker, ABT-639, effectively reduces nociceptive and neuropathic pain in rats. Biochem Pharmacol. 2014 Jun 15;89(4):536-44. doi: 10.1016/j.bcp.2014.03.015. Epub 2014 Apr 12. PMID: 24726441. |
| In vitro protocol: | 1. Wang MX, Liu X, Li JM, Liu L, Lu W, Chen GC. Inhibition of CACNA1H can alleviate endoplasmic reticulum stress and reduce myocardial cell apoptosis caused by myocardial infarction. Eur Rev Med Pharmacol Sci. 2020 Dec;24(24):12887-12895. doi: 10.26355/eurrev_202012_24192. PMID: 33378039. 2. Hu J, Wu Q, Wang Z, Hong J, Chen R, Li B, Hu Z, Hu X, Zhang M. Inhibition of CACNA1H attenuates doxorubicin-induced acute cardiotoxicity by affecting endoplasmic reticulum stress. Biomed Pharmacother. 2019 Dec;120:109475. doi: 10.1016/j.biopha.2019.109475. Epub 2019 Sep 30. PMID: 31580970. |
| In vivo protocol: | 1. Zhang Q, Xia Z, Joshi S, Scott VE, Jarvis MF. Optimization of ADME Properties for Sulfonamides Leading to the Discovery of a T-Type Calcium Channel Blocker, ABT-639. ACS Med Chem Lett. 2015 Apr 28;6(6):641-4. doi: 10.1021/acsmedchemlett.5b00023. PMID: 26101566; PMCID: PMC4468402. 2. Jarvis MF, Scott VE, McGaraughty S, Chu KL, Xu J, Niforatos W, Milicic I, Joshi S, Zhang Q, Xia Z. A peripherally acting, selective T-type calcium channel blocker, ABT-639, effectively reduces nociceptive and neuropathic pain in rats. Biochem Pharmacol. 2014 Jun 15;89(4):536-44. doi: 10.1016/j.bcp.2014.03.015. Epub 2014 Apr 12. PMID: 24726441. |
1: Zhang Q, Xia Z, Joshi S, Scott VE, Jarvis MF. Optimization of ADME Properties for Sulfonamides Leading to the Discovery of a T-Type Calcium Channel Blocker, ABT-639. ACS Med Chem Lett. 2015 Apr 28;6(6):641-4. doi: 10.1021/acsmedchemlett.5b00023. eCollection 2015 Jun 11. PubMed PMID: 26101566; PubMed Central PMCID: PMC4468402.
2: Ziegler D, Duan WR, An G, Thomas JW, Nothaft W. A randomized double-blind, placebo-, and active-controlled study of T-type calcium channel blocker ABT-639 in patients with diabetic peripheral neuropathic pain. Pain. 2015 Oct;156(10):2013-20. doi: 10.1097/j.pain.0000000000000263. PubMed PMID: 26067585.
3: Serra J, Duan WR, Locke C, Solà R, Liu W, Nothaft W. Effects of a T-type calcium channel blocker, ABT-639, on spontaneous activity in C-nociceptors in patients with painful diabetic neuropathy: a randomized controlled trial. Pain. 2015 Nov;156(11):2175-83. doi: 10.1097/j.pain.0000000000000249. PubMed PMID: 26035253.
4: An G, Liu W, Duan WR, Nothaft W, Awni W, Dutta S. Erratum to: population pharmacokinetics and exposure-uric acid analyses after single and multiple doses of ABT-639, a calcium channel blocker, in healthy volunteers. AAPS J. 2015 Mar;17(2):481-92. doi: 10.1208/s12248-015-9725-9. PubMed PMID: 25676842; PubMed Central PMCID: PMC4365100.
5: An G, Liu W, Duan WR, Nothaft W, Awni W, Dutta S. Population pharmacokinetics and exposure-uric acid analyses after single and multiple doses of ABT-639, a calcium channel blocker, in healthy volunteers. AAPS J. 2015 Mar;17(2):416-26. doi: 10.1208/s12248-014-9709-1. Epub 2015 Jan 8. Erratum in: AAPS J. 2015 Mar;17(2):481-92. PubMed PMID: 25567367; PubMed Central PMCID: PMC4365099.
6: Jarvis MF, Scott VE, McGaraughty S, Chu KL, Xu J, Niforatos W, Milicic I, Joshi S, Zhang Q, Xia Z. A peripherally acting, selective T-type calcium channel blocker, ABT-639, effectively reduces nociceptive and neuropathic pain in rats. Biochem Pharmacol. 2014 Jun 15;89(4):536-44. doi: 10.1016/j.bcp.2014.03.015. Epub 2014 Apr 12. PubMed PMID: 24726441.
