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
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
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 |
mg/mL |
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 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
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.
