RTI-5152-12

RTI-5152-12
臨床資料
其他名稱	WW-12 (patent)
藥物類別	ACKR3 (CXCR7) agonist; Opioid modulator
识别信息
	IUPAC命名法 [(3E,4R)-3-ethylidene-1-pentylpiperidin-4-yl]-(1H-indol-2-yl)methanone; ;
CAS号	2794983-92-7
PubChem CID	155927823;
化学信息
化学式	C21H28N2O
摩尔质量	324.47 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES CCCCCN1CC[C@H](/C(=C\C)/C1)C(=O)C2=CC3=CC=CC=C3N2;
	InChI InChI=1S/C21H28N2O/c1-3-5-8-12-23-13-11-18(16(4-2)15-23)21(24)20-14-17-9-6-7-10-19(17)22-20/h4,6-7,9-10,14,18,22H,3,5,8,11-13,15H2,1-2H3/b16-4-/t18-/m1/s1; Key:MUZOMTWDNLINCG-QBSXKKPKSA-N;

RTI-5152-12（或称为WW-12）是一种含氮有机化合物，化学式C₂₁H₂₈N₂O，可作为趋化因子受体 ACKR3（CXCR-7）的小分子激动剂^[1]^[2]^[3]。

参考文献

^ Palmer CB, Meyrath M, Canals M, Kostenis E, Chevigné A, Szpakowska M. Atypical opioid receptors: unconventional biology and therapeutic opportunities. Pharmacol Ther. May 2022, 233: 108014. PMID 34624426. doi:10.1016/j.pharmthera.2021.108014. Interestingly, ACKR3 has recently been demonstrated to be the main GPCR target of conolidine (Szpakowska et al., 2021), a natural analgesic alkaloid found in the bark of the tropical flowering shrub Tabernaemontana divaricate, which is used in traditional Chinese medicine to treat fever and pain (Tarselli et al., 2011). [...] Systematic chemical modifications of conolidine resulted in an analogue compound, RTI-5152-12, with 15-fold improved potency towards ACKR3. Notably, conolidine and RTI-5152-12 function similarly to LIH383 and conolidine's analgesic activity was proposed to rely on the inhibition of the scavenging functions of ACKR3 increasing the availability of analgesia-inducing endogenous opioid peptides for the classical ORs.
^ Szpakowska M, Decker AM, Meyrath M, Palmer CB, Blough BE, Namjoshi OA, Chevigné A. The natural analgesic conolidine targets the newly identified opioid scavenger ACKR3/CXCR7. Signal Transduct Target Ther. June 2021, 6 (1): 209. PMC 8169647 . PMID 34075018. doi:10.1038/s41392-021-00548-w.
^ WO 2022136486A1,Andy Chevigné, Martyna Szpakowska, Ojas Namjoshi, Bruce Edward Blough, Ann Marie Decker, Max Marc Roger Meyrath,「Conolidine Analogues As Selective ACKR3 Modulators for the Treatment of Cancer and Cardiovascular Diseases」,发表于30 June 2022

外部链接

The Good Drug Guide - Conolidine / RTI-5152-12 - David Pearce

[PalmerMeyrathCanals2022-1] Palmer CB, Meyrath M, Canals M, Kostenis E, Chevigné A, Szpakowska M. Atypical opioid receptors: unconventional biology and therapeutic opportunities. Pharmacol Ther. May 2022, 233: 108014. PMID 34624426. doi:10.1016/j.pharmthera.2021.108014. Interestingly, ACKR3 has recently been demonstrated to be the main GPCR target of conolidine (Szpakowska et al., 2021), a natural analgesic alkaloid found in the bark of the tropical flowering shrub Tabernaemontana divaricate, which is used in traditional Chinese medicine to treat fever and pain (Tarselli et al., 2011). [...] Systematic chemical modifications of conolidine resulted in an analogue compound, RTI-5152-12, with 15-fold improved potency towards ACKR3. Notably, conolidine and RTI-5152-12 function similarly to LIH383 and conolidine's analgesic activity was proposed to rely on the inhibition of the scavenging functions of ACKR3 increasing the availability of analgesia-inducing endogenous opioid peptides for the classical ORs.

[SzpakowskaDeckerMeyrath2021-2] Szpakowska M, Decker AM, Meyrath M, Palmer CB, Blough BE, Namjoshi OA, Chevigné A. The natural analgesic conolidine targets the newly identified opioid scavenger ACKR3/CXCR7. Signal Transduct Target Ther. June 2021, 6 (1): 209. PMC 8169647 . PMID 34075018. doi:10.1038/s41392-021-00548-w.

[WO2022136486A1-3] WO 2022136486A1,Andy Chevigné, Martyna Szpakowska, Ojas Namjoshi, Bruce Edward Blough, Ann Marie Decker, Max Marc Roger Meyrath,「Conolidine Analogues As Selective ACKR3 Modulators for the Treatment of Cancer and Cardiovascular Diseases」,发表于30 June 2022

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