KC01

• CAS: 1646795-59-6
• Catalog Number: ACM1646795596
• Category: Inhibitors
• Molecular Weight: 365.56
• Molecular Formula: C22H39NO3
• Description: KC01 is a covalent inhibitor of ABHD16A. ABHD16A is a phosphatidylserine (PS) lipase that generates lyso-PS in mammalian systems. KC01 can deplete lysoPSs from cells, including lymphoblasts derived from subjects with PHARC.
• Synonyms: KC01; K C01; K-C01
• IUPAC Name: (Z)-6-(2-oxo-4-tridecyloxetan-3-ylidene)hexanamide
• Canonical SMILES: O=C(N)CCCC/C=C1C(OC\1CCCCCCCCCCCCC)=O
• InChI: InChI=1S/C22H39NO3/c1-2-3-4-5-6-7-8-9-10-11-14-17-20-19(22(25)26-20)16-13-12-15-18-21(23)24/h16,20H,2-15,17-18H2,1H3,(H2,23,24)/b19-16-
• InChI Key: RJBBAPPWVJEOMC-MNDPQUGUSA-N
• Solubility: Soluble in DMSO (15 mg/mL)
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: ABHD16A inhibitor.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 72.28; H, 10.75; N, 3.83; O, 13.13
• Exact Mass: 365.293
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: Lysophosphatidylserines (lyso-PSs) are a class of signaling lipids that regulate immunological and neurological processes. It was determined that ABHD12 is a major brain lyso-PS lipase, implicating lyso-PSs in the neurological disease polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and cataract (PHARC), which is caused by null mutations in the ABHD12 gene. Activity-based profiling was coupled with pharmacological and genetic methods to annotate the poorly characterized enzyme ABHD16A as a phosphatidylserine (PS) lipase that generates lyso-PS in mammalian systems. KC01, a small-molecule inhibitor of ABHD16A, depleted lyso-PSs from cells, including lymphoblasts derived from subjects with PHARC. Treatment with KC01 (1 μM, 4 h) blocked the PS lipase activity of membrane fractions from COLO205, K562, and MCF7 cell lines (Supplementary Fig. 9). KC01 also reversed the elevated lyso-PS production observed in ABHD12-null cells derived from a PHARC subject. These findings provide evidence for an interplay between ABHD16A and ABHD12 in the potential regulation of PHARC.; Reference: Nat Chem Biol. 2015 Feb;11(2):164-71. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301979/
• In Vivo Activity: To more directly address the role of ABHD16A in vivo, an ABHD16A-/- mouse model was established (Supplementary Fig. 25). The PS lipase activity of brain membrane lysates from ABHD16A-/- mice was greatly decreased compared to ABHD16A+/+ and +/- lysates (Fig. 5c). The brain lipid profiles for ABHD16A+/+, +/-, and -/- mice were evaluated and it was found that ABHD16A-/- mice exhibited substantial reductions in most of the measured lyso-PSs (Fig. 5d). Similar reductions in lyso-PSs were found in spinal cord of ABHD16A-/- mice (Supplementary Fig. 29), which also exhibited lower PS lipase activity compared to ABHD16A+/+ mice (Supplementary Fig. 29). To gain further confidence that KC01 produced its pharmacological effects by blocking ABHD16A, macrophages from ABHD16A-/- mice were treated with this inhibitor. No changes were observed under basal conditions or LPS stimulation in cellular or secreted lyso-PS and other measured lipids, or in secreted proinflammatory cytokines (IL-6 and TNF-α), in KC01-treated ABHD16A-/- macrophages (Supplementary Fig. 32 and Supplementary Table 1).; Reference: Nat Chem Biol. 2015 Feb;11(2):164-71. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301979/
• Shipping: 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.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).