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| 25mg |
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| 100mg |
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Purity: ≥98%
ABT-639 is a new potent, peripherally acting, selective T-type Ca2+ channel blocker that blocks recombinant human T-type (Cav3.2) Ca2+ channels in a voltage-dependent fashion (IC50=2 μM) and attenuates low voltage-activated (LVA) currents in rat DRG neurons (IC50=8 μM). ABT-639 is significantly less active at other Ca2+ channels (e.g. Cav1.2 and Cav2.2) (IC50>30 mM). Following oral administration ABT-639 produced dose-dependent antinociception in a rat model of knee joint pain (ED₅₀ = 2 mg/kg, p.o.). ABT-639 (10-100 mg/kg, p.o.) also increased tactile allodynia thresholds in multiple models of neuropathic pain (e.g. spinal nerve ligation, CCI, and vincristine-induced). [corrected]. ABT-639 did not attenuate hyperalgesia in inflammatory pain models induced by complete Freund's adjuvant or carrageenan. At higher doses (e.g. 100-300 mg/kg) ABT-639 did not significantly alter hemodynamic or psychomotor function. The antinociceptive profile of ABT-639 provides novel insights into the role of peripheral T-type (Ca(v)3.2) channels in chronic pain states.
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| ln Vivo |
ABT-639 attenuates low voltage-activated (LVA) currents in rat DRG neurons (IC50=8 μM) and blocks recombinant human T-type (Cav3.2) Ca2+ channels in a voltage-dependent manner (IC50=2 μM). ABT -639 exhibits significantly lower activity at other Ca2+ channels (IC50>30 mM), such as Cav1.2 and Cav2.2. In rodents, ABT-639 exhibits low protein binding (88.9%), a low brain:plasma ratio (0.05:1), and high oral bioavailability (%F=73). In a rat model of knee joint pain, oral administration of ABT-639 results in dose-dependent antinociception (ED50=2 mg/kg, po). In various models of neuropathic pain, such as spinal nerve ligation, CCI, vincristine-induced, and capsaicin secondary hypersensitivity, ABT-639 (10-100 mg/kg, po) also raises tactile allodynia thresholds. In inflammatory pain models induced by carrageenan or complete Freund's adjuvant, ABT-639 does not reduce hyperalgesia. Higher doses of ABT-639 (such as 100–300 mg/kg) have no discernible effects on hemodynamic or psychomotor function. Novel insights into the function of peripheral T-type (Cav3.2) channels in chronic pain states are offered by the antinociceptive profile of ABT-639[1].
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| Additional Infomation |
ABT-639 is under investigation in clinical trial NCT01345045 (A Multicenter Study Comparing the Analgesic Effects and Safety of ABT-639 Compared to Placebo in Subjects With Diabetic Neuropathic Pain).
T-type Calcium Channel Blocker ABT-639 is an orally bioavailable, CaV3.2 T-type calcium channel blocker with potential anti-hyperalgesic activity. Upon oral administration, ABT-639 selectively binds to and blocks the CaV3.2 isoform of the low voltage-gated T-type calcium channels located in peripheral sensory neurons. This prevents the influx of calcium ions into the cell upon membrane depolarization. The inhibition of both neuronal hyperexcitability and firing of nociceptive, peripheral sensory neurons induces an anti-nociceptive effect. The expression of the CaV3.2 T-type channels plays a key role in nociceptive and neuropathic pain. |
| Molecular Formula |
C20H20CLF2N3O3S
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| Molecular Weight |
455.91
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| Exact Mass |
455.088
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| CAS # |
1235560-28-7
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| Related CAS # |
ABT-639 hydrochloride;1235560-31-2
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| PubChem CID |
46851313
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
612.2±65.0 °C at 760 mmHg
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| Flash Point |
324.0±34.3 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.653
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
737
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1C[C@@H]2CN(CCN2C1)C(=O)C3=CC(=C(C=C3Cl)F)S(=O)(=O)NC4=CC=CC=C4F
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| InChi Key |
AGPIHNZOZNKRGT-CYBMUJFWSA-N
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| 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
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| Chemical Name |
5-[(8aR)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-2-carbonyl]-4-chloro-2-fluoro-N-(2-fluorophenyl)benzenesulfonamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1934 mL | 10.9671 mL | 21.9342 mL | |
| 5 mM | 0.4387 mL | 2.1934 mL | 4.3868 mL | |
| 10 mM | 0.2193 mL | 1.0967 mL | 2.1934 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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