K252a

K252a
	IUPAC名 (9S-(9α,10β,12α))-2,3,9,10,11,12-hexahydro-10-hydroxy-10-(methoxycarbonyl)-9-methyl-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocin-1-one
識別情報
CAS登録番号	99533-80-9
PubChem	3035817
ChemSpider	2299962
UNII	IV7H45AM5B
J-GLOBAL ID	200907012660216403
ChEMBL	CHEMBL281948
IUPHAR/BPS	336
	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;
特性
化学式	C27H21N3O5
モル質量	467.47 g mol−1
その他の溶媒への溶解度	DMSO、ジクロロメタン、メタノールに可溶
	特記なき場合、データは常温 (25 °C)・常圧 (100 kPa) におけるものである。

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.
^ ^a ^b 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.

この項目は、化学に関連した書きかけの項目です。この項目を加筆・訂正などしてくださる協力者を求めています（プロジェクト:化学／Portal:化学）。

[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] 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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