m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG02289)
Name
Geldanamycin
Synonyms
GDM; GMY; Geldanamicin; Geldanomycin; Geldaramycin; Antibiotic U 29135; BODIPY-labeled Geldanamycin; Geldanamycin (9CI); Geldanamycin, Streptomyces hygroscopicus; U-29135; Antibiotic (U-29,135); [(8E,12E,14Z)-6-hydroxy-5,11,21-trimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate; [(8E,12Z,14E)-6-hydroxy-5,11,21-trimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate; [(8Z,12Z,14Z)-6-hydroxy-5,11,21-trimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate; [(3R,5R,6S,7R,10R,11R)-6-hydroxy-5,11,21-trimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate; [(3R,5S,6R,7S,10R,11R)-6-hydroxy-5,11,21-trimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate; [(3R,5S,6R,7S,10S,11S)-6-hydroxy-5,11,21-trimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate; [(3S,5S,6R,7S,8E,10R,11S,12Z,14E)-6-Hydroxy-5,11,21-trimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-8,12,14,18,21-pentaen-10-yl] carbamate; [(3R,5R,6S,7R,8E,10R,11R,12Z,14E)-6-hydroxy-5,11,21-trimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate; [(3R,5S,6R,7S,8E,10R,11R,12Z,14E)-6-hydroxy-5,11,21-trimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate; [(3R,5S,6R,7S,8E,10S,11S,12Z,14E)-6-hydroxy-5,11,21-trimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate; [(3S,5S,6R,7S,8E,10S,11S,12Z,14E)-6-hydroxy-5,11,21-trimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate; (4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-hydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate; (6-hydroxy-5,11,21-trimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl) carbamate; [8S-(4E,6Z,8R*,9R*,10E,12R*,13S*,14R*,16S*)]-9-[(Aminocarbonyl)oxy]-13-hydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-2-azabicyclo[16.3.1]docosa-4,6,10,18,21-pentaene-3,20,22-trione; 2-Azabicyclo[16.3.1]docosa-4,6,10,18,21-pentaene-3,20,22-trione, 9,13-dihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-, 9-carbamate (8CI); 2-Azabicyclo[16.3.1]docosane, geldanamycin deriv.
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Status
Discontinued in Phase 2
Structure
Formula
C29H40N2O9
InChI
1S/C29H40N2O9/c1-15-11-19-25(34)20(14-21(32)27(19)39-7)31-28(35)16(2)9-8-10-22(37-5)26(40-29(30)36)18(4)13-17(3)24(33)23(12-15)38-6/h8-10,13-15,17,22-24,26,33H,11-12H2,1-7H3,(H2,30,36)(H,31,35)/b10-8-,16-9+,18-13+/t15-,17+,22+,23+,24-,26+/m1/s1
InChIKey
QTQAWLPCGQOSGP-KSRBKZBZSA-N
PubChem CID
5288382
TTD Drug ID
D03PKI
Target Gene(s) and Their Upstream m6A Regulator, Together with the Effect of Target Gene(s) in Drug Response
The target genes involved in drug-target interaction (such as drug-metabolizing enzymes, drug transporters and therapeutic targets) and drug-mediated cell death signaling (including modulating DNA damage and repair capacity, escaping from drug-induced apoptosis, autophagy, cellular metabolic reprogramming, oncogenic bypass signaling, cell microenvironment, cell stemness, etc.) could be regulated by m6A regulator(s) and affected their corresponding drug response. You can browse detailed information on drug-related target gene(s) mediated by m6A regulators.
Heat shock protein 90 alpha (HSP90A)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Heat shock protein 90 alpha (HSP90A) is a therapeutic target for Geldanamycin. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of Geldanamycin through regulating the expression of Heat shock protein 90 alpha (HSP90A). [1], [2]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Heat shock protein 90 alpha (HSP90A) is a therapeutic target for Geldanamycin. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of Geldanamycin through regulating the expression of Heat shock protein 90 alpha (HSP90A). [1], [2]
YTH domain-containing family protein 2 (YTHDF2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Heat shock protein 90 alpha (HSP90A) is a therapeutic target for Geldanamycin. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of Geldanamycin through regulating the expression of Heat shock protein 90 alpha (HSP90A). [2], [3]
References
Ref 1 m6A RNA Methylation Controls Proliferation of Human Glioma Cells by Influencing Cell Apoptosis. Cytogenet Genome Res. 2019;159(3):119-125. doi: 10.1159/000499062. Epub 2019 Oct 23.
Ref 2 US patent application no. 2013,0023,420, Susceptibility to hsp90-inhibitors.
Ref 3 Modification of N6-methyladenosine RNA methylation on heat shock protein expression. PLoS One. 2018 Jun 14;13(6):e0198604. doi: 10.1371/journal.pone.0198604. eCollection 2018.