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: 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. PMID: 25567367; PMCID: PMC4365099.
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.
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: 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):2013-2020. doi: 10.1097/j.pain.0000000000000263. PMID: 26067585; PMCID: PMC4770341.
5: Wallace M, Duan R, Liu W, Locke C, Nothaft W. A Randomized, Double-Blind, Placebo-Controlled, Crossover Study of the T-Type Calcium Channel Blocker ABT-639 in an Intradermal Capsaicin Experimental Pain Model in Healthy Adults. Pain Med. 2016 Mar;17(3):551-560. doi: 10.1093/pm/pnv068. Epub 2015 Dec 16. PMID: 26814294.
6: 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. Erratum for: AAPS J. 2015 Mar;17(2):416-26. PMID: 25676842; PMCID: PMC4365100.
7: 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):2175-2183. doi: 10.1097/j.pain.0000000000000249. PMID: 26035253.
8: Tibbs GR, Posson DJ, Goldstein PA. Voltage-Gated Ion Channels in the PNS: Novel Therapies for Neuropathic Pain? Trends Pharmacol Sci. 2016 Jul;37(7):522-542. doi: 10.1016/j.tips.2016.05.002. Epub 2016 May 24. PMID: 27233519.
9: 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.
10: Liu S, Ba Y, Li C, Xu G. Inactivation of CACNA1H induces cell apoptosis by initiating endoplasmic reticulum stress in glioma. Transl Neurosci. 2023 May 26;14(1):20220285. doi: 10.1515/tnsci-2022-0285. PMID: 37250140; PMCID: PMC10224624.
11: 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.
12: Picard E, Carvalho FA, Agosti F, Bourinet E, Ardid D, Eschalier A, Daulhac L, Mallet C. Inhibition of Cav 3.2 calcium channels: A new target for colonic hypersensitivity associated with low-grade inflammation. Br J Pharmacol. 2019 Apr;176(7):950-963. doi: 10.1111/bph.14608. Epub 2019 Mar 11. PMID: 30714145; PMCID: PMC6433640.
13: Wu H, Xie X, Sun M, Chen M, Tao X, Fang X, Meng X, Wei W, Yu M. Modification of mesenchymal stem cells by HMGB1 promotes the activity of Cav3.2 T-type calcium channel via PKA/β-catenin/γ-cystathionase pathway. Stem Cell Res Ther. 2022 Jan 10;13(1):4. doi: 10.1186/s13287-021-02677-z. PMID: 35012644; PMCID: PMC8744322.
14: Grundy L, Tay C, Christie S, Harrington AM, Castro J, Cardoso FC, Lewis RJ, Zagorodnyuk V, Brierley SM. The T-type calcium channel Ca V 3.2 regulates bladder afferent responses to mechanical stimuli. Pain. 2023 May 1;164(5):1012-1026. doi: 10.1097/j.pain.0000000000002795. Epub 2022 Oct 21. PMID: 36279179; PMCID: PMC10108591.
15: Teleb M, Zhang FX, Huang J, Gadotti VM, Farghaly AM, AboulWafa OM, Zamponi GW, Fahmy H. Synthesis and biological evaluation of novel N3-substituted dihydropyrimidine derivatives as T-type calcium channel blockers and their efficacy as analgesics in mouse models of inflammatory pain. Bioorg Med Chem. 2017 Mar 15;25(6):1926-1938. doi: 10.1016/j.bmc.2017.02.015. Epub 2017 Feb 13. PMID: 28233679.
16: Picard E, Kerckhove N, François A, Boudieu L, Billard E, Carvalho FA, Bogard G, Gosset P, Bourdier J, Aissouni Y, Bourinet E, Eschalier A, Daulhac L, Mallet C. Role of T CD4+ cells, macrophages, C-low threshold mechanoreceptors and spinal Cav 3.2 channels in inflammation and related pain-like symptoms in murine inflammatory models. Br J Pharmacol. 2023 Feb;180(4):385-400. doi: 10.1111/bph.15956. Epub 2022 Nov 14. PMID: 36131381.
