WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H561252
CAS#: 1646795-59-6
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.
Hodoodo Cat#: H561252
Name: KC01
CAS#: 1646795-59-6
Chemical Formula: C22H39NO3
Exact Mass: 365.29
Molecular Weight: 365.560
Elemental Analysis: C, 72.28; H, 10.75; N, 3.83; O, 13.13
Synonym: KC01; K C01; K-C01
IUPAC/Chemical Name: (Z)-6-(2-oxo-4-tridecyloxetan-3-ylidene)hexanamide
InChi Key: RJBBAPPWVJEOMC-MNDPQUGUSA-N
InChi Code: 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-
SMILES Code: O=C(N)CCCC/C=C1C(OC\1CCCCCCCCCCCCC)=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 (15mg / mL)
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
More Info:
| Biological target: | ABHD16A inhibitor. |
| 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/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 5.0 | 13.68 | |
| DMSO | 5.0 | 13.68 | |
| Ethanol | 16.0 | 43.77 | |
| Ethanol:PBS (pH 7.2) (1:5) | 0.5 | 1.37 |
The following data is based on the product molecular weight 365.56 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. Kamat SS, Camara K, Parsons WH, Chen DH, Dix MM, Bird TD, Howell AR, Cravatt BF. Immunomodulatory lysophosphatidylserines are regulated by ABHD16A and ABHD12 interplay. Nat Chem Biol. 2015 Feb;11(2):164-71. doi: 10.1038/nchembio.1721. Epub 2015 Jan 12. PMID: 25580854; PMCID: PMC4301979. |
| In vitro protocol: | 1. Kamat SS, Camara K, Parsons WH, Chen DH, Dix MM, Bird TD, Howell AR, Cravatt BF. Immunomodulatory lysophosphatidylserines are regulated by ABHD16A and ABHD12 interplay. Nat Chem Biol. 2015 Feb;11(2):164-71. doi: 10.1038/nchembio.1721. Epub 2015 Jan 12. PMID: 25580854; PMCID: PMC4301979. |
| In vivo protocol: | 1. Kamat SS, Camara K, Parsons WH, Chen DH, Dix MM, Bird TD, Howell AR, Cravatt BF. Immunomodulatory lysophosphatidylserines are regulated by ABHD16A and ABHD12 interplay. Nat Chem Biol. 2015 Feb;11(2):164-71. doi: 10.1038/nchembio.1721. Epub 2015 Jan 12. PMID: 25580854; PMCID: PMC4301979. |
1. Kamat SS, Camara K, Parsons WH, Chen DH, Dix MM, Bird TD, Howell AR, Cravatt BF. Immunomodulatory lysophosphatidylserines are regulated by ABHD16A and ABHD12 interplay. Nat Chem Biol. 2015 Feb;11(2):164-71.
2. Parsons, William H.; Kolar, Matthew J.; Kamat, Siddhesh S.; Cognetta, Armand B., III; Hulce, Jonathan J.; Saez, Enrique; Kahn, Barbara B.; Saghatelian, Alan; Cravatt, Benjamin F. AIG1 and ADTRP are atypical integral membrane hydrolases that degrade bioactive FAHFAs. Nature Chemical Biology (2016), 12(5), 367-372.
