Details
Stereochemistry | RACEMIC |
Molecular Formula | C18H31O3.Na |
Molecular Weight | 318.4267 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 2 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].CCCCC\C=C/C\C=C/CCCCCCC(O)C([O-])=O
InChI
InChIKey=VFXKYDDSDQXKLC-NBTZWHCOSA-M
InChI=1S/C18H32O3.Na/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17(19)18(20)21;/h6-7,9-10,17,19H,2-5,8,11-16H2,1H3,(H,20,21);/q;+1/p-1/b7-6-,10-9-;
ABTL 0812 is a autophagy inducer that acts via PI3K/Akt/mTOR pathway and has a dual mechanism of action. ABTL-0812 is a first-in-class small molecule, orally administered that binds to the nuclear receptors PPARα/γ inducing TRIB3 overexpression which blocks Akt activation, the central kinase of the PI3K/Akt/mTOR pathway, and inducing PPAR-dependent Endoplasmic Reticular Stress (ER-stress). The combination of TRIB3-mediated inhibition of the PI3K/Akt/mTOR pathway and the ER-Stress induction results in an autophagy-mediated cancer cell death. In animal cancer models ABTL0812 is efficacious as single agent with an excellent safety profile in a broad spectrum of cancer types: lung, endometrial and pancreatic cancer and neuroblastoma. ABTL0812 is also active on cells resistant to other targeted therapies, on tumor stem cells and inhibits metastasis formation. Preliminary results show promising immunomodulatory effects. ABTL0812 is currently in phase 2 clinical trials in Europe in patients with endometrial cancer or squamous cell lung cancer, as a first-line treatment in combination with chemotherapy and as a maintenance treatment after the chemotherapy cycles. The study is being conducted in leading cancer hospitals in Spain and France. This same phase 2 study was also approved by the US FDA in December 2017. In addition, the FDA approved the protocol for a phase 2 study in pancreatic cancer in January 2018. ABTL-0812 has also received Orphan Drug Designations (ODD) for pancreatic cancer, biliary cancer and the pediatric cancer neuroblastoma by the FDA in the USA and by the EMA in Europe.
Originator
Approval Year
Sample Use Guides
Advanced solid tumors:ABTL-0812 was dosed daily, by the oral route, in 28-day cycles. The study included a 4-cohort dose escalation, in a 3+3 dose escalating design, followed by an expansion cohort. Recommended Phase II was 1300 mg tid.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26671995
In vitro radioligand displacement assays using purified proteins showed that ABTL-0812 binds PPARα and PPARγ ligand-binding pockets with Ki values of 7.1 umol/L and 4.7 umol/L, respectively
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
652418
Created by
admin on Sat Dec 16 12:44:43 GMT 2023 , Edited by admin on Sat Dec 16 12:44:43 GMT 2023
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EU-Orphan Drug |
EU/3/18/2121
Created by
admin on Sat Dec 16 12:44:43 GMT 2023 , Edited by admin on Sat Dec 16 12:44:43 GMT 2023
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FDA ORPHAN DRUG |
489315
Created by
admin on Sat Dec 16 12:44:43 GMT 2023 , Edited by admin on Sat Dec 16 12:44:43 GMT 2023
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FDA ORPHAN DRUG |
543816
Created by
admin on Sat Dec 16 12:44:43 GMT 2023 , Edited by admin on Sat Dec 16 12:44:43 GMT 2023
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91666690
Created by
admin on Sat Dec 16 12:44:43 GMT 2023 , Edited by admin on Sat Dec 16 12:44:43 GMT 2023
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PRIMARY | |||
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X1840C8161
Created by
admin on Sat Dec 16 12:44:43 GMT 2023 , Edited by admin on Sat Dec 16 12:44:43 GMT 2023
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PRIMARY | |||
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100000177209
Created by
admin on Sat Dec 16 12:44:43 GMT 2023 , Edited by admin on Sat Dec 16 12:44:43 GMT 2023
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PRIMARY |
ACTIVE MOIETY
SUBSTANCE RECORD