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Details

Stereochemistry ABSOLUTE
Molecular Formula C27H21N3O5
Molecular Weight 467.4738
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of K252A

SMILES

C[C@]12[C@](C[C@]([H])(n3c4ccccc4c5c6c(CN=C6O)c7c8ccccc8n1c7c53)O2)(C(=O)OC)O

InChI

InChIKey=KOZFSFOOLUUIGY-SOLYNIJKSA-N
InChI=1S/C27H21N3O5/c1-26-27(33,25(32)34-2)11-18(35-26)29-16-9-5-3-7-13(16)20-21-15(12-28-24(21)31)19-14-8-4-6-10-17(14)30(26)23(19)22(20)29/h3-10,18,33H,11-12H2,1-2H3,(H,28,31)/t18-,26+,27+/m1/s1

HIDE SMILES / InChI

Molecular Formula C27H21N3O5
Molecular Weight 467.4738
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

K-252a, a metabolite isolated from the culture broth of Nocardiopsis sp. K-252a, was found to exhibit an extremely potent inhibitory activity on protein kinase C. The IC50 value was 32.9 nM. K252a is a potent inhibitor of various protein kinases including Protein kinase A, Protein kinase C and Protein kinase G. It acts by competition with the ATP binding site with Ki values of 18-25 nM. K252a also acts as a specific and potent inhibitor (IC50 = 3 nM) of Trk receptors and thus selectively blocks the effects of nerve growth factor (NGF) on PC12 cells. At lower concentrations, K252a can act as a neuroprotective compound, promoting survival of primary neuronal cultures. This alkaloid induces apoptosis and cell cycle arrest by inhibiting Cdc2 and Cdc25.4 Recently, K252a was found to improve psoriasis in a SCID mouse-human skin model and to suppress referred mechanical hypersensitivity and neuropeptide up-regulation associated with acute pancreatitis.

CNS Activity

Curator's Comment:: K252a does not cross the blood-brain barrier

Approval Year

PubMed

PubMed

TitleDatePubMed
K-252b, c and d, potent inhibitors of protein kinase C from microbial origin.
1986 Aug
Effects of a protein kinase C inhibitor, K-252a, on human polymorphonuclear neutrophil responsiveness.
1988 May 16
K252a and CEP1347 are neuroprotective compounds that inhibit mixed-lineage kinase-3 and induce activation of Akt and ERK.
2002 Dec 20
Synthesis, modeling, and in vitro activity of (3'S)-epi-K-252a analogues. Elucidating the stereochemical requirements of the 3'-sugar alcohol on trkA tyrosine kinase activity.
2005 Jun 2
Effect of construct design on MAPKAP kinase-2 activity, thermodynamic stability and ligand-binding affinity.
2006 May 15
Patents

Patents

Sample Use Guides

1.0 g K-252a (CT 327) cream will be applied to one target lesion twice daily
Route of Administration: Topical
In Vitro Use Guide
K-252a inhibited PMN PKC (IC50 = 0.58 uM), and caused a concentration-dependent (0.1-10 uM) inhibition of degranulation elicited with the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), the lipid agonists, 5(S), 12(R)-dihydroxy-5,14-cis-8,10-trans eicosatetraenoic acid (LTB4) and acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC), and phorbol 12-myristate 13-acetate.
Substance Class Chemical
Created
by admin
on Sat Jun 26 09:32:05 UTC 2021
Edited
by admin
on Sat Jun 26 09:32:05 UTC 2021
Record UNII
IV7H45AM5B
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
K252A
Common Name English
K 252A
Common Name English
(+)-SF 2370
Common Name English
9,12-EPOXY-1H-DIINDOLO(1,2,3-FG:3',2',1'-KL)PYRROLO(3,4-I)(1,6)BENZODIAZOCINE-10-CARBOXYLIC ACID, 2,3,9,10,11,12-HEXAHYDRO-10-HYDROXY-9-METHYL-1-OXO-, METHYL ESTER, (9S-(9.ALPHA.,10.BETA.,12.ALPHA.))-
Common Name English
ANTIBIOTIC SF 2370
Common Name English
ANTIBIOTIC K 252A
Common Name English
PROTEIN KINASE INHIBITOR K252A
Common Name English
K-252A
Code English
K 252
Common Name English
SF 2370
Common Name English
(+)-ANTIBIOTIC K 252A
Common Name English
(+)-K 252A
Common Name English
ANTIBIOTIC SF 2370, (+)-
Common Name English
ANTIBIOTIC K 252A, (+)-
Common Name English
(+)-ANTIBIOTIC SF 2370
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2089
Created by admin on Sat Jun 26 09:32:06 UTC 2021 , Edited by admin on Sat Jun 26 09:32:06 UTC 2021
Code System Code Type Description
WIKIPEDIA
K252A
Created by admin on Sat Jun 26 09:32:06 UTC 2021 , Edited by admin on Sat Jun 26 09:32:06 UTC 2021
PRIMARY
NCI_THESAURUS
C1382
Created by admin on Sat Jun 26 09:32:06 UTC 2021 , Edited by admin on Sat Jun 26 09:32:06 UTC 2021
PRIMARY
PUBCHEM
3035817
Created by admin on Sat Jun 26 09:32:06 UTC 2021 , Edited by admin on Sat Jun 26 09:32:06 UTC 2021
PRIMARY
DRUG BANK
DB02152
Created by admin on Sat Jun 26 09:32:06 UTC 2021 , Edited by admin on Sat Jun 26 09:32:06 UTC 2021
PRIMARY
FDA UNII
IV7H45AM5B
Created by admin on Sat Jun 26 09:32:06 UTC 2021 , Edited by admin on Sat Jun 26 09:32:06 UTC 2021
PRIMARY
CAS
99533-80-9
Created by admin on Sat Jun 26 09:32:06 UTC 2021 , Edited by admin on Sat Jun 26 09:32:06 UTC 2021
PRIMARY