Drug Details

General Information of the Drug (ID: DR5808)
Name
MG262
Synonyms
MG-262; PS-III; MG262; UNII-549V4DP94W; 179324-22-2; CHEMBL114388; 549V4DP94W; boro-LLL; ((5S,8S,11R)-5,8-diisobutyl-13-methyl-3,6,9-trioxo-1-phenyl-2-oxa-4,7,10-triazatetradecan-11-yl)boronic acid; Z-Leu-Leu-Leu-B(OH)2 (MG262); [(1R)-1-[[(2S)-2-[[(2S)-2-(benzyloxycarbonylamino)-4-methyl-pentanoyl]amino]-4-methyl-pentanoyl]amino]-3-methyl-butyl]boronic acid; MG 262; SCHEMBL12384366; DTXSID80170795; BDBM50069984; ZINC169998630; [(1R)-3-methyl-1-[[(2S)-4-methyl-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]pentanoyl]amino]butyl]boronic acid; A8179; Q27261199; L-Leucinamide, N-[(phenylmethoxy)carbonyl]-L-leucyl-N1-[(1R)-1-borono-3-methylbutyl]-; (R)-1-((S)-2-((S)-2-(benzyloxycarbonyl)-4-methylpentanamido)-4-methylpentanamido)-3-methylbutylboronic acid
    Click to Show/Hide
Molecular Type
Small molecule
Disease Ovarian cancer [ICD-11: 2C73] Investigative [1]
Structure
Click to Download Mol
2D MOL

3D MOL

    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C25H42BN3O6
PubChem CID
490002
Canonical SMILES
B(C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)OCC1=CC=CC=C1)(O)O
InChI
1S/C25H42BN3O6/c1-16(2)12-20(24(31)29-22(26(33)34)14-18(5)6)27-23(30)21(13-17(3)4)28-25(32)35-15-19-10-8-7-9-11-19/h7-11,16-18,20-22,33-34H,12-15H2,1-6H3,(H,27,30)(H,28,32)(H,29,31)/t20-,21-,22-/m0/s1
InChIKey
MWKOOGAFELWOCD-FKBYEOEOSA-N
CAS Number
CAS 179324-22-2
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Gambogic acid      Garcinia morella     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
H22 CVCL_H613 Hepatocellular carcinoma of the mouse Mus musculus
                    In-vivo Model Murine hepatoma H22 cells (10 * 106) suspended in 0.2 ml of serum-free RPMI 1640 were inoculated s.c. in the left armpit of each mouse.
                    Experimental
                    Result(s)		 The combination of natural product gambogic acid and the proteasome inhibitor MG132 or MG262 results in a synergistic inhibitory effect on growth of malignant cells and tumors in allograft animal models and there was no apparent systemic toxicity observed in the animals treated with the combination.
Target and Pathway
Target(s) Apoptosis regulator Bcl-2 (BCL-2)  Molecule Info  [3]
KEGG Pathway NF-kappa B signaling pathway Click to Show/Hide
2 HIF-1 signaling pathway
3 Sphingolipid signaling pathway
4 Protein processing in endoplasmic reticulum
5 PI3K-Akt signaling pathway
6 Apoptosis
7 Adrenergic signaling in cardiomyocytes
8 Focal adhesion
9 Neurotrophin signaling pathway
10 Cholinergic synapse
11 Amyotrophic lateral sclerosis (ALS)
12 Toxoplasmosis
13 Tuberculosis
14 Hepatitis B
15 Epstein-Barr virus infection
16 Pathways in cancer
17 MicroRNAs in cancer
18 Colorectal cancer
19 Prostate cancer
20 Small cell lung cancer
NetPath Pathway IL5 Signaling Pathway Click to Show/Hide
2 TCR Signaling Pathway
3 IL2 Signaling Pathway
4 IL3 Signaling Pathway
5 Leptin Signaling Pathway
6 RANKL Signaling Pathway
7 TSLP Signaling Pathway
Panther Pathway Apoptosis signaling pathway Click to Show/Hide
2 Oxidative stress response
3 CCKR signaling map ST
Pathway Interaction Database Role of Calcineurin-dependent NFAT signaling in lymphocytes Click to Show/Hide
2 IL2-mediated signaling events
3 IL2 signaling events mediated by PI3K
4 Ceramide signaling pathway
5 Direct p53 effectors
6 RXR and RAR heterodimerization with other nuclear receptor
7 ATF-2 transcription factor network
8 C-MYB transcription factor network
9 HIV-1 Nef: Negative effector of Fas and TNF-alpha
10 Caspase Cascade in Apoptosis
11 Signaling events mediated by Stem cell factor receptor (c-Kit)
12 EPO signaling pathway
13 IL2 signaling events mediated by STAT5
14 Validated targets of C-MYC transcriptional repression
Reactome Activation of BAD and translocation to mitochondria Click to Show/Hide
2 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
3 The NLRP1 inflammasome
WikiPathways DNA Damage Response (only ATM dependent) Click to Show/Hide
2 Senescence and Autophagy in Cancer
3 IL-2 Signaling Pathway
4 FAS pathway and Stress induction of HSP regulation
5 Focal Adhesion
6 Kit receptor signaling pathway
7 IL-3 Signaling Pathway
8 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
9 Apoptosis
10 Nanoparticle triggered autophagic cell death
11 Amyotrophic lateral sclerosis (ALS)
12 Integrated Pancreatic Cancer Pathway
13 Corticotropin-releasing hormone
14 Interleukin-11 Signaling Pathway
15 Prostate Cancer
16 miR-targeted genes in muscle cell - TarBase
17 miR-targeted genes in lymphocytes - TarBase
18 miR-targeted genes in leukocytes - TarBase
19 Integrated Breast Cancer Pathway
20 Integrated Cancer pathway
21 Intrinsic Pathway for Apoptosis
22 Apoptosis Modulation and Signaling
23 TP53 Network
24 Influenza A virus infection
25 IL-5 Signaling Pathway
References
Reference 1 [Effect of extracellular signal regulated kinase signal pathway on apoptosis induced by MG262 in ovarian cancer cells]. Zhonghua Fu Chan Ke Za Zhi. 2008 Sep;43(9):690-4.
Reference 2 Gambogic acid enhances proteasome inhibitor-induced anticancer activity. Cancer Lett. 2011 Feb 28;301(2):221-8.
Reference 3 HA14-1, a small molecule inhibitor of Bcl-2, bypasses chemoresistance in leukaemia cells. Leuk Res. 2007 Jun;31(6):859-63.
 Download Picture         KEGG Link