m6A-centered Drug Response Information

General Information of the Drug (ID: M6ADRUG0066)
Name
R-2HG
Synonyms
(R)-2-Hydroxypentanedioic acid; 13095-47-1; D-2-Hydroxyglutaric acid; (R)-2-hydroxyglutaric acid; (R)-Hydroxyglutarate; (R)-2-hydroxyglutarate; Pentanedioic acid, 2-hydroxy-, (2R)-; CHEMBL1614745; CHEBI:32796; D-2-Hydroxyglutarate; Glutaric acid, 2-hydroxy-; d-alpha-hydroxyglutaric acid; D-Hydroxyglutarate; 2HG; D-a-Hydroxyglutarate; 2-hydroxy-D-Glutarate; (R)-a-Hydroxyglutarate; delta-2-Hydroxyglutarate; D-a-Hydroxyglutaric acid; 2-hydroxy-delta-Glutarate; D-; A-Hydroxyglutaric acid; (2R)-hydroxyglutaric acid; 2-hydroxy-D-Glutaric acid; (R)-alpha-Hydroxyglutarate; delta-alpha-Hydroxyglutarate; SCHEMBL8032; (R)-a-Hydroxyglutaric acid; delta-2-Hydroxyglutaric acid; (R)-2-hydroxy-Pentanedioate; 2-hydroxy-delta-Glutaric acid; (R)-alpha-Hydroxyglutaric acid; delta-alpha-Hydroxyglutaric acid; (R)-2-hydroxy-Pentanedioic acid; DTXSID80897218; ZINC402968; BDBM50361471; AKOS027325193; FD21404; BS-50252; HY-113038; CS-0059411; C01087; 93397C3E-3CE9-4FEA-A2ED-8F6FA59A1FEA; Q27104222; Z2217110365; 636-67-9
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Status Investigative [1]
Structure
Formula
C5H8O5
InChI
InChI=1S/C5H8O5/c6-3(5(9)10)1-2-4(7)8/h3,6H,1-2H2,(H,7,8)(H,9,10)/t3-/m1/s1
InChIKey
HWXBTNAVRSUOJR-GSVOUGTGSA-N
PubChem CID
439391
Full List of m6A Targets Related to This Drug
CCAAT/enhancer-binding protein alpha (CEBPA)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary This work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/MYC/CCAAT/enhancer-binding protein alpha (CEBPA) signaling.High levels of FTO sensitize leukemia cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling.
Responsed Disease Glioma ICD-11: 2A00.0
 Disease Info 
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Cell Process Glutamine metabolism
Cell apoptosis
In-vitro Model 8-MG-BA Glioblastoma Homo sapiens CVCL_1052
A-172 Glioblastoma Homo sapiens CVCL_0131
DK-MG Glioblastoma Homo sapiens CVCL_1173
GaMG Glioblastoma Homo sapiens CVCL_1226
HEL Erythroleukemia Homo sapiens CVCL_0001
Jurkat T acute lymphoblastic leukemia Homo sapiens CVCL_0065
KOCL-45 B acute lymphoblastic leukemia Homo sapiens CVCL_3993
KOCL-48 Childhood acute monocytic leukemia Homo sapiens CVCL_6867
KOCL-50 B acute lymphoblastic leukemia Homo sapiens CVCL_6866
KOCL-51 B acute lymphoblastic leukemia Homo sapiens CVCL_6865
KOCL-69 B acute lymphoblastic leukemia Homo sapiens CVCL_3995
KOPN-1 B acute lymphoblastic leukemia Homo sapiens CVCL_3937
LN-18 Glioblastoma Homo sapiens CVCL_0392
LN-229 Glioblastoma Homo sapiens CVCL_0393
MA9.3 (MA9.3)
MA9.6ITD (MLL-AF9 plus FLT3-ITD)
MA9.6RAS (MLL-AF9 plus NRasG12D)
MA9.6 (MLL-AF9)
MA9.6ITD (MLL-AF9 plus FLT3-ITD)
MA9.6RAS (MLL-AF9 plus NRasG12D)
ME-1 [Human leukemia] Adult acute myeloid leukemia Homo sapiens CVCL_2110
ML-2 Adult acute myeloid leukemia Homo sapiens CVCL_1418
MV4-11 Childhood acute monocytic leukemia Homo sapiens CVCL_0064
NB4 Acute promyelocytic leukemia Homo sapiens CVCL_0005
NOMO-1 Adult acute monocytic leukemia Homo sapiens CVCL_1609
PL21 Familial adenomatous polyposis Homo sapiens CVCL_JM48
T98G Glioblastoma Homo sapiens CVCL_0556
THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
U-87MG ATCC Glioblastoma Homo sapiens CVCL_0022
U-937 Adult acute monocytic leukemia Homo sapiens CVCL_0007
In-vivo Model For R-2HG injection mouse models, sensitive (NOMO-1 and MA9.3ITD) or resistant (MA9.3RAS) cells were injected into NSGS or NRGS intravenously, and then R-2HG (6mg/kg body weight) or PBS were injected once daily through tail vein for 12 consecutive days starting from day 11 post xeno-transplantation.
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary This work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/MYC/CCAAT/enhancer-binding protein alpha (CEBPA) signaling.High levels of FTO sensitize leukemia cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling.
Responsed Disease Leukaemia ICD-11: 2B33.4
 Disease Info 
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Cell Process Glutamine metabolism
Cell apoptosis
In-vitro Model 8-MG-BA Glioblastoma Homo sapiens CVCL_1052
A-172 Glioblastoma Homo sapiens CVCL_0131
DK-MG Glioblastoma Homo sapiens CVCL_1173
GaMG Glioblastoma Homo sapiens CVCL_1226
HEL Erythroleukemia Homo sapiens CVCL_0001
Jurkat T acute lymphoblastic leukemia Homo sapiens CVCL_0065
KOCL-45 B acute lymphoblastic leukemia Homo sapiens CVCL_3993
KOCL-48 Childhood acute monocytic leukemia Homo sapiens CVCL_6867
KOCL-50 B acute lymphoblastic leukemia Homo sapiens CVCL_6866
KOCL-51 B acute lymphoblastic leukemia Homo sapiens CVCL_6865
KOCL-69 B acute lymphoblastic leukemia Homo sapiens CVCL_3995
KOPN-1 B acute lymphoblastic leukemia Homo sapiens CVCL_3937
LN-18 Glioblastoma Homo sapiens CVCL_0392
LN-229 Glioblastoma Homo sapiens CVCL_0393
MA9.3 (MA9.3)
MA9.6ITD (MLL-AF9 plus FLT3-ITD)
MA9.6RAS (MLL-AF9 plus NRasG12D)
MA9.6 (MLL-AF9)
MA9.6ITD (MLL-AF9 plus FLT3-ITD)
MA9.6RAS (MLL-AF9 plus NRasG12D)
ME-1 [Human leukemia] Adult acute myeloid leukemia Homo sapiens CVCL_2110
ML-2 Adult acute myeloid leukemia Homo sapiens CVCL_1418
MV4-11 Childhood acute monocytic leukemia Homo sapiens CVCL_0064
NB4 Acute promyelocytic leukemia Homo sapiens CVCL_0005
NOMO-1 Adult acute monocytic leukemia Homo sapiens CVCL_1609
PL21 Familial adenomatous polyposis Homo sapiens CVCL_JM48
T98G Glioblastoma Homo sapiens CVCL_0556
THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
U-87MG ATCC Glioblastoma Homo sapiens CVCL_0022
U-937 Adult acute monocytic leukemia Homo sapiens CVCL_0007
In-vivo Model For R-2HG injection mouse models, sensitive (NOMO-1 and MA9.3ITD) or resistant (MA9.3RAS) cells were injected into NSGS or NRGS intravenously, and then R-2HG (6mg/kg body weight) or PBS were injected once daily through tail vein for 12 consecutive days starting from day 11 post xeno-transplantation.
Myc proto-oncogene protein (MYC)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary This work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/Myc proto-oncogene protein (MYC)/CEBPA signaling.High levels of FTO sensitize leukemia cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling.
Responsed Disease Glioma ICD-11: 2A00.0
 Disease Info 
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Cell Process Glutamine metabolism
Cell apoptosis
In-vitro Model 8-MG-BA Glioblastoma Homo sapiens CVCL_1052
A-172 Glioblastoma Homo sapiens CVCL_0131
DK-MG Glioblastoma Homo sapiens CVCL_1173
GaMG Glioblastoma Homo sapiens CVCL_1226
HEL Erythroleukemia Homo sapiens CVCL_0001
Jurkat T acute lymphoblastic leukemia Homo sapiens CVCL_0065
KOCL-45 B acute lymphoblastic leukemia Homo sapiens CVCL_3993
KOCL-48 Childhood acute monocytic leukemia Homo sapiens CVCL_6867
KOCL-50 B acute lymphoblastic leukemia Homo sapiens CVCL_6866
KOCL-51 B acute lymphoblastic leukemia Homo sapiens CVCL_6865
KOCL-69 B acute lymphoblastic leukemia Homo sapiens CVCL_3995
KOPN-1 B acute lymphoblastic leukemia Homo sapiens CVCL_3937
LN-18 Glioblastoma Homo sapiens CVCL_0392
LN-229 Glioblastoma Homo sapiens CVCL_0393
MA9.3 (MA9.3)
MA9.6ITD (MLL-AF9 plus FLT3-ITD)
MA9.6RAS (MLL-AF9 plus NRasG12D)
MA9.6 (MLL-AF9)
MA9.6ITD (MLL-AF9 plus FLT3-ITD)
MA9.6RAS (MLL-AF9 plus NRasG12D)
ME-1 [Human leukemia] Adult acute myeloid leukemia Homo sapiens CVCL_2110
ML-2 Adult acute myeloid leukemia Homo sapiens CVCL_1418
MV4-11 Childhood acute monocytic leukemia Homo sapiens CVCL_0064
NB4 Acute promyelocytic leukemia Homo sapiens CVCL_0005
NOMO-1 Adult acute monocytic leukemia Homo sapiens CVCL_1609
PL21 Familial adenomatous polyposis Homo sapiens CVCL_JM48
T98G Glioblastoma Homo sapiens CVCL_0556
THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
U-87MG ATCC Glioblastoma Homo sapiens CVCL_0022
U-937 Adult acute monocytic leukemia Homo sapiens CVCL_0007
In-vivo Model For R-2HG injection mouse models, sensitive (NOMO-1 and MA9.3ITD) or resistant (MA9.3RAS) cells were injected into NSGS or NRGS intravenously, and then R-2HG (6mg/kg body weight) or PBS were injected once daily through tail vein for 12 consecutive days starting from day 11 post xeno-transplantation.
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary This work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/Myc proto-oncogene protein (MYC)/CEBPA signaling.High levels of FTO sensitize leukemia cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling.
Responsed Disease Leukaemia ICD-11: 2B33.4
 Disease Info 
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Cell Process Glutamine metabolism
Cell apoptosis
In-vitro Model 8-MG-BA Glioblastoma Homo sapiens CVCL_1052
A-172 Glioblastoma Homo sapiens CVCL_0131
DK-MG Glioblastoma Homo sapiens CVCL_1173
GaMG Glioblastoma Homo sapiens CVCL_1226
HEL Erythroleukemia Homo sapiens CVCL_0001
Jurkat T acute lymphoblastic leukemia Homo sapiens CVCL_0065
KOCL-45 B acute lymphoblastic leukemia Homo sapiens CVCL_3993
KOCL-48 Childhood acute monocytic leukemia Homo sapiens CVCL_6867
KOCL-50 B acute lymphoblastic leukemia Homo sapiens CVCL_6866
KOCL-51 B acute lymphoblastic leukemia Homo sapiens CVCL_6865
KOCL-69 B acute lymphoblastic leukemia Homo sapiens CVCL_3995
KOPN-1 B acute lymphoblastic leukemia Homo sapiens CVCL_3937
LN-18 Glioblastoma Homo sapiens CVCL_0392
LN-229 Glioblastoma Homo sapiens CVCL_0393
MA9.3 (MA9.3)
MA9.6ITD (MLL-AF9 plus FLT3-ITD)
MA9.6RAS (MLL-AF9 plus NRasG12D)
MA9.6 (MLL-AF9)
MA9.6ITD (MLL-AF9 plus FLT3-ITD)
MA9.6RAS (MLL-AF9 plus NRasG12D)
ME-1 [Human leukemia] Adult acute myeloid leukemia Homo sapiens CVCL_2110
ML-2 Adult acute myeloid leukemia Homo sapiens CVCL_1418
MV4-11 Childhood acute monocytic leukemia Homo sapiens CVCL_0064
NB4 Acute promyelocytic leukemia Homo sapiens CVCL_0005
NOMO-1 Adult acute monocytic leukemia Homo sapiens CVCL_1609
PL21 Familial adenomatous polyposis Homo sapiens CVCL_JM48
T98G Glioblastoma Homo sapiens CVCL_0556
THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
U-87MG ATCC Glioblastoma Homo sapiens CVCL_0022
U-937 Adult acute monocytic leukemia Homo sapiens CVCL_0007
In-vivo Model For R-2HG injection mouse models, sensitive (NOMO-1 and MA9.3ITD) or resistant (MA9.3RAS) cells were injected into NSGS or NRGS intravenously, and then R-2HG (6mg/kg body weight) or PBS were injected once daily through tail vein for 12 consecutive days starting from day 11 post xeno-transplantation.
References
Ref 1 R-2-hydroxyglutarate attenuates aerobic glycolysis in leukemia by targeting the FTO/m(6)A/PFKP/LDHB axis. Mol Cell. 2021 Mar 4;81(5):922-939.e9. doi: 10.1016/j.molcel.2020.12.026.
Ref 2 R-2HG Exhibits Anti-tumor Activity by Targeting FTO/m(6)A/MYC/CEBPA Signaling. Cell. 2018 Jan 11;172(1-2):90-105.e23. doi: 10.1016/j.cell.2017.11.031. Epub 2017 Dec 14.