YM-254890

YM-254890
Identifiers
	IUPAC name [(1R)-1-[(3S,6S,9S,12S,18R,21S,22R)-21-acetamido-18-benzyl-3-[(1R)-1-methoxyethyl]-4,9,10,12,16,22-hexamethyl-15-methylidene-2,5,8,11,14,17,20-heptaoxo-1,19-dioxa-4,7,10,13,16-pentazacyclodocos-6-yl]-2-methylpropyl] (2S,3R)-2-acetamido-3-hydroxy-4-methylpentanoate;
CAS Number	568580-02-9;
PubChem CID	9919454;
IUPHAR/BPS	9335;
ChemSpider	8095094;
ChEMBL	ChEMBL4288881;
Chemical and physical data
Formula	C46H69N7O15
Molar mass	960.092 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@@H]1[C@@H](C(=O)O[C@@H](C(=O)N(C(=C)C(=O)N[C@H](C(=O)N([C@H](C(=O)N[C@H](C(=O)N([C@H](C(=O)O1)[C@@H](C)OC)C)[C@@H](C(C)C)OC(=O)[C@H]([C@@H](C(C)C)O)NC(=O)C)C)C)C)C)CC2=CC=CC=C2)NC(=O)C;
	InChI InChI=1S/C46H69N7O15/c1-22(2)37(56)34(49-30(11)55)45(63)68-38(23(3)4)35-43(61)53(14)36(28(9)65-15)46(64)66-27(8)33(48-29(10)54)44(62)67-32(21-31-19-17-16-18-20-31)42(60)52(13)25(6)39(57)47-24(5)41(59)51(12)26(7)40(58)50-35/h16-20,22-24,26-28,32-38,56H,6,21H2,1-5,7-15H3,(H,47,57)(H,48,54)(H,49,55)(H,50,58)/t24-,26-,27+,28+,32+,33-,34-,35-,36-,37+,38+/m0/s1; Key:QVYLWCAYZGFGNF-WBWCVGBTSA-N;

YM-254890 is a macrolide antibiotic derived from Chromobacterium species.^[1]^[2]^[3]^[4] It is used as a pharmacological research compound which acts as a selective inhibitor of G_q mediated signalling.^[5]^[6]^[7]^[8]^[9] However the claimed selectivity for G_q has been disputed.^[10]

References

^ Mizuno N, Itoh H (2009). "Functions and regulatory mechanisms of Gq-signaling pathways". Neuro-Signals. 17 (1): 42–54. doi:10.1159/000186689. PMID 19212139. S2CID 556083.
^ Kamato D, Thach L, Bernard R, Chan V, Zheng W, Kaur H, et al. (2015). "Structure, Function, Pharmacology, and Therapeutic Potential of the G Protein, Gα/q,11". Frontiers in Cardiovascular Medicine. 2: 14. doi:10.3389/fcvm.2015.00014. PMC 4671355. PMID 26664886.
^ Kamato D, Mitra P, Davis F, Osman N, Chaplin R, Cabot PJ, et al. (April 2017). "Ga_q proteins: molecular pharmacology and therapeutic potential". Cellular and Molecular Life Sciences. 74 (8): 1379–1390. doi:10.1007/s00018-016-2405-9. PMC 11107756. PMID 27815595. S2CID 253596970.
^ Hermes C, König GM, Crüsemann M (December 2021). "The chromodepsins - chemistry, biology and biosynthesis of a selective Gq inhibitor natural product family". Natural Product Reports. 38 (12): 2276–2292. doi:10.1039/D1NP00005E. PMID 33998635. S2CID 234748014.
^ Xiong XF, Zhang H, Underwood CR, Harpsøe K, Gardella TJ, Wöldike MF, et al. (November 2016). "Total synthesis and structure-activity relationship studies of a series of selective G protein inhibitors". Nature Chemistry. 8 (11): 1035–1041. Bibcode:2016NatCh...8.1035X. doi:10.1038/nchem.2577. PMC 5559716. PMID 27768111.
^ Xiong XF, Zhang H, Boesgaard MW, Underwood CR, Bräuner-Osborne H, Strømgaard K (April 2019). "Structure-Activity Relationship Studies of the Natural Product G_q/11 Protein Inhibitor YM-254890". ChemMedChem. 14 (8): 865–870. doi:10.1002/cmdc.201900018. PMID 30790465. S2CID 73469968.
^ Li J, Ge Y, Huang JX, Strømgaard K, Zhang X, Xiong XF (May 2020). "Heterotrimeric G Proteins as Therapeutic Targets in Drug Discovery". Journal of Medicinal Chemistry. 63 (10): 5013–5030. doi:10.1021/acs.jmedchem.9b01452. PMID 31841625. S2CID 209389142.
^ Zhang H, Nielsen AL, Strømgaard K (January 2020). "Recent achievements in developing selective G_q inhibitors". Medicinal Research Reviews. 40 (1): 135–157. doi:10.1002/med.21598. PMID 31218731. S2CID 195192483.
^ Schlegel JG, Tahoun M, Seidinger A, Voss JH, Kuschak M, Kehraus S, et al. (April 2021). "Macrocyclic Gq Protein Inhibitors FR900359 and/or YM-254890-Fit for Translation?". ACS Pharmacology & Translational Science. 4 (2): 888–897. doi:10.1021/acsptsci.1c00021. PMC 8033771. PMID 33860209. S2CID 233258488.
^ Peng Q, Shen J (2019). "YM-254890 is a General Inhibitor of G Proteins". The FASEB Journal. 33 (S1): 503.7. doi:10.1096/fasebj.2019.33.1_supplement.503.7. S2CID 241743171.

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[1] Mizuno N, Itoh H (2009). "Functions and regulatory mechanisms of Gq-signaling pathways". Neuro-Signals. 17 (1): 42–54. doi:10.1159/000186689. PMID 19212139. S2CID 556083.

[2] Kamato D, Thach L, Bernard R, Chan V, Zheng W, Kaur H, et al. (2015). "Structure, Function, Pharmacology, and Therapeutic Potential of the G Protein, Gα/q,11". Frontiers in Cardiovascular Medicine. 2: 14. doi:10.3389/fcvm.2015.00014. PMC 4671355. PMID 26664886.

[3] Kamato D, Mitra P, Davis F, Osman N, Chaplin R, Cabot PJ, et al. (April 2017). "Ga_q proteins: molecular pharmacology and therapeutic potential". Cellular and Molecular Life Sciences. 74 (8): 1379–1390. doi:10.1007/s00018-016-2405-9. PMC 11107756. PMID 27815595. S2CID 253596970.

[4] Hermes C, König GM, Crüsemann M (December 2021). "The chromodepsins - chemistry, biology and biosynthesis of a selective Gq inhibitor natural product family". Natural Product Reports. 38 (12): 2276–2292. doi:10.1039/D1NP00005E. PMID 33998635. S2CID 234748014.

[5] Xiong XF, Zhang H, Underwood CR, Harpsøe K, Gardella TJ, Wöldike MF, et al. (November 2016). "Total synthesis and structure-activity relationship studies of a series of selective G protein inhibitors". Nature Chemistry. 8 (11): 1035–1041. Bibcode:2016NatCh...8.1035X. doi:10.1038/nchem.2577. PMC 5559716. PMID 27768111.

[6] Xiong XF, Zhang H, Boesgaard MW, Underwood CR, Bräuner-Osborne H, Strømgaard K (April 2019). "Structure-Activity Relationship Studies of the Natural Product G_q/11 Protein Inhibitor YM-254890". ChemMedChem. 14 (8): 865–870. doi:10.1002/cmdc.201900018. PMID 30790465. S2CID 73469968.

[7] Li J, Ge Y, Huang JX, Strømgaard K, Zhang X, Xiong XF (May 2020). "Heterotrimeric G Proteins as Therapeutic Targets in Drug Discovery". Journal of Medicinal Chemistry. 63 (10): 5013–5030. doi:10.1021/acs.jmedchem.9b01452. PMID 31841625. S2CID 209389142.

[8] Zhang H, Nielsen AL, Strømgaard K (January 2020). "Recent achievements in developing selective G_q inhibitors". Medicinal Research Reviews. 40 (1): 135–157. doi:10.1002/med.21598. PMID 31218731. S2CID 195192483.

[9] Schlegel JG, Tahoun M, Seidinger A, Voss JH, Kuschak M, Kehraus S, et al. (April 2021). "Macrocyclic Gq Protein Inhibitors FR900359 and/or YM-254890-Fit for Translation?". ACS Pharmacology & Translational Science. 4 (2): 888–897. doi:10.1021/acsptsci.1c00021. PMC 8033771. PMID 33860209. S2CID 233258488.

[10] Peng Q, Shen J (2019). "YM-254890 is a General Inhibitor of G Proteins". The FASEB Journal. 33 (S1): 503.7. doi:10.1096/fasebj.2019.33.1_supplement.503.7. S2CID 241743171.

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Identifiers

IUPAC name [(1R)-1-[(3S,6S,9S,12S,18R,21S,22R)-21-acetamido-18-benzyl-3-[(1R)-1-methoxyethyl]-4,9,10,12,16,22-hexamethyl-15-methylidene-2,5,8,11,14,17,20-heptaoxo-1,19-dioxa-4,7,10,13,16-pentazacyclodocos-6-yl]-2-methylpropyl] (2S,3R)-2-acetamido-3-hydroxy-4-methylpentanoate
CAS Number	568580-02-9
PubChem CID	9919454
IUPHAR/BPS	9335
ChemSpider	8095094
ChEMBL	ChEMBL4288881
Chemical and physical data
Formula	C₄₆H₆₉N₇O₁₅
Molar mass	960.092 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES C[C@@H]1[C@@H](C(=O)O[C@@H](C(=O)N(C(=C)C(=O)N[C@H](C(=O)N([C@H](C(=O)N[C@H](C(=O)N([C@H](C(=O)O1)[C@@H](C)OC)C)[C@@H](C(C)C)OC(=O)[C@H]([C@@H](C(C)C)O)NC(=O)C)C)C)C)C)CC2=CC=CC=C2)NC(=O)C
InChI InChI=1S/C46H69N7O15/c1-22(2)37(56)34(49-30(11)55)45(63)68-38(23(3)4)35-43(61)53(14)36(28(9)65-15)46(64)66-27(8)33(48-29(10)54)44(62)67-32(21-31-19-17-16-18-20-31)42(60)52(13)25(6)39(57)47-24(5)41(59)51(12)26(7)40(58)50-35/h16-20,22-24,26-28,32-38,56H,6,21H2,1-5,7-15H3,(H,47,57)(H,48,54)(H,49,55)(H,50,58)/t24-,26-,27+,28+,32+,33-,34-,35-,36-,37+,38+/m0/s1 Key:QVYLWCAYZGFGNF-WBWCVGBTSA-N