K252a

K252a
物質名
	優先IUPAC名 Methyl (13S,14R,16R)-14-hydroxy-13-methyl-5-oxo-6,7,13,14,15,16-hexahydro-5H-13,16-epoxydiindolo[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-i][1,6]benzodiazocine-14-carboxylate
識別情報
CAS登録番号	99533-80-9 ;
ChEMBL	ChEMBL281948 ;
ChemSpider	2299962 ;
ECHA InfoCard	100.167.781
IUPHAR/BPS	336;
PubChem CID	3035817;
UNII	IV7H45AM5B ;
CompTox Dashboard (EPA)	DTXSID40880065 ;
	InChI 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 Key: KOZFSFOOLUUIGY-CYBHFKQVSA-N ;
性質
化学式	C27H21N3O5
モル質量	467.481 g·mol−1
その他溶媒への溶解度	ジメチルスルホキシド、ジクロロメタン、メタノールに溶ける
	特記無き場合、データは標準状態 (25 °C [77 °F], 100 kPa) におけるものである。 verify (what is ?)

K252aは、土壌菌Nocardiopisis sp. から単離されたアルカロイドである。このスタウロスポリン構造類縁体は極めて強力なCaMキナーゼおよびホスホリラーゼキナーゼの細胞透過性を有する阻害剤である（IC₅₀はそれぞれ1.8および1.7 nmol/L）。高濃度では、セリン/スレオニンプロテインキナーゼの有効な阻害剤でもある（IC₅₀は10〜30 nmol/L）^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]。

K252aはC2マウス筋芽細胞において筋肉分化を促進すると報告されており^[6]、ラット褐色細胞腫PC12細胞の神経分化をtrkチロシンキナーゼ活性の阻害によって妨害することが示されている^[10]。K252aはNGFで誘導されるTrk Aのチロシンリン酸化を阻害する。

1995年にK252aの全合成が報告されている^[11]。

脚注

↑ K252a from Fermentek
↑ Rüegg UT, Burgess GM (1989). “Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases”. Trends Pharmacol. Sci. 10 (6): 218-220. doi:10.1016/0165-6147(89)90263-0. PMID 2672462.
↑ Elliott LH, Wilkinson SE, Sedgwick AD, Hill CH, Lawton G, Davis PD, Nixon JS (1990). “K252a is a potent and selective inhibitor of phosphorylase kinase”. Biochem. Biophys. Res. Commun. 171 (1): 148-154. doi:10.1016/0006-291X(90)91369-4. PMID 2393389.
↑ Simpson DL, Dickens G, Doll S, Koizumi S, Tocco M, Okuda O, Oshima M, Rudkin BB, Brightman M, Guroff G (1991). “Differentiation of PC12 cells with K-ras: comparison with nerve growth factor”. J. Neurosci. Res. 28 (4): 486-496. doi:10.1002/jnr.490280405. PMID 1651400.
↑ Chin LS, Murray SF, Doherty PF, Singh SK (1999). “K252a induces cell cycle arrest and apoptosis by inhibiting Cdc2 and Cdc25c”. Cancer Invest. 17 (6): 391-395. doi:10.3109/07357909909021430. PMID 10434949.
1 2 Tapley P, Lamballe F, Barbacid M (1992). “K252a is a selective inhibitor of the tyrosine protein kinase activity of the trk family of oncogenes and neurotrophin receptors”. Oncogene 7 (2): 371-381. PMID 1312698.
↑ Hashimoto S (1988). “K-252a, a potent protein kinase inhibitor, blocks nerve growth factor-induced neurite outgrowth and changes in the phosphorylation of proteins in PC12h cells”. J. Cell. Biol. 107 (4): 1531-1539. doi:10.1083/jcb.107.4.1531. PMC 2115256. PMID 2844830.
↑ Kase H, Iwahashi K, Nakanishi S, Matsuda Y, Yamada K, Takahashi M, Murakata C, Sato A, Kaneko M (1987). “K-252 compounds, novel and potent inhibitors of protein kinase C and cyclic nucleotide-dependent protein kinases”. Biochem. Biophys. Res. Commun. 142 (2): 436-440. doi:10.1016/0006-291X(87)90293-2. PMID 3028414.
↑ Hirayama E, Sasao N, Yoshimasu S, Kim J (2001). “K252a, an indrocarbazole derivative, causes the membrane of myoblasts to enter a fusion-capable state”. Biochem. Biophys. Res. Commun. 285 (5): 1237-1243. doi:10.1006/bbrc.2001.5327. PMID 11478789.
↑ Borasio GD (1990). “Differential effects of the protein kinase inhibitor K-252a on the in vitro survival of chick embryonic neurons”. Neurosci. Lett. 108 (1-2): 207-212. doi:10.1016/0304-3940(90)90732-O. PMID 2304631.
↑ Wood JL, Stoltz BM, Dietrich H-J (1995). “Total synthesis of (+)- and (−)-K252a”. J. Am. Chem. Soc. 117 (41): 10413–10414. doi:10.1021/ja00146a039.

[1] K252a from Fermentek

[2] Rüegg UT, Burgess GM (1989). “Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases”. Trends Pharmacol. Sci. 10 (6): 218-220. doi:10.1016/0165-6147(89)90263-0. PMID 2672462.

[3] Elliott LH, Wilkinson SE, Sedgwick AD, Hill CH, Lawton G, Davis PD, Nixon JS (1990). “K252a is a potent and selective inhibitor of phosphorylase kinase”. Biochem. Biophys. Res. Commun. 171 (1): 148-154. doi:10.1016/0006-291X(90)91369-4. PMID 2393389.

[4] Simpson DL, Dickens G, Doll S, Koizumi S, Tocco M, Okuda O, Oshima M, Rudkin BB, Brightman M, Guroff G (1991). “Differentiation of PC12 cells with K-ras: comparison with nerve growth factor”. J. Neurosci. Res. 28 (4): 486-496. doi:10.1002/jnr.490280405. PMID 1651400.

[5] Chin LS, Murray SF, Doherty PF, Singh SK (1999). “K252a induces cell cycle arrest and apoptosis by inhibiting Cdc2 and Cdc25c”. Cancer Invest. 17 (6): 391-395. doi:10.3109/07357909909021430. PMID 10434949.

[Tapley-6] 1 2 Tapley P, Lamballe F, Barbacid M (1992). “K252a is a selective inhibitor of the tyrosine protein kinase activity of the trk family of oncogenes and neurotrophin receptors”. Oncogene 7 (2): 371-381. PMID 1312698.

[7] Hashimoto S (1988). “K-252a, a potent protein kinase inhibitor, blocks nerve growth factor-induced neurite outgrowth and changes in the phosphorylation of proteins in PC12h cells”. J. Cell. Biol. 107 (4): 1531-1539. doi:10.1083/jcb.107.4.1531. PMC 2115256. PMID 2844830.

[8] Kase H, Iwahashi K, Nakanishi S, Matsuda Y, Yamada K, Takahashi M, Murakata C, Sato A, Kaneko M (1987). “K-252 compounds, novel and potent inhibitors of protein kinase C and cyclic nucleotide-dependent protein kinases”. Biochem. Biophys. Res. Commun. 142 (2): 436-440. doi:10.1016/0006-291X(87)90293-2. PMID 3028414.

[9] Hirayama E, Sasao N, Yoshimasu S, Kim J (2001). “K252a, an indrocarbazole derivative, causes the membrane of myoblasts to enter a fusion-capable state”. Biochem. Biophys. Res. Commun. 285 (5): 1237-1243. doi:10.1006/bbrc.2001.5327. PMID 11478789.

[10] Borasio GD (1990). “Differential effects of the protein kinase inhibitor K-252a on the in vitro survival of chick embryonic neurons”. Neurosci. Lett. 108 (1-2): 207-212. doi:10.1016/0304-3940(90)90732-O. PMID 2304631.

[11] Wood JL, Stoltz BM, Dietrich H-J (1995). “Total synthesis of (+)- and (−)-K252a”. J. Am. Chem. Soc. 117 (41): 10413–10414. doi:10.1021/ja00146a039.

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