ABTL0812 (α-hydroxylinoleic acid) is a small-molecule, experimental cancer drug being developed by Ability Pharmaceuticals.[1]

ABTL0812
Clinical data
Other namesα-Hydroxylinoleic acid; 2-Hydroxylinoleic acid; ABTL-0812
Legal status
Legal status
  • Investigational
Identifiers
  • (9Z,12Z)-2-Hydroxyoctadeca-9,12-dienoic acid
CAS Number
PubChem CID
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC18H32O3
Molar mass296.451 g·mol−1
3D model (JSmol)
  • CCCCC/C=C\C/C=C\CCCCCCC(C(=O)O)O

History

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In 2015, Ability announced that it had received orphan drug designation (ODD) for pediatric cancer neuroblastoma from the European Medical Agency (EMA) and the US Food and Drug Administration (FDA).[1] Also in 2016 a preclinical study confirmed that ABTL0812 was well tolerated.[2] In December 2016 the company announced ODD for the treatment of pancreatic cancer.[1]

Mechanism of action

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One mechanism of action is the activation of the PPAR receptors and the TRIB3 gene, leading to inhibition of the Akt/mTOR pathway. This pathway is excessively activated in most human cancers, supporting tumor growth. It is a principal target of various new anti-tumour drugs. Tumor cells are killed viva autophagy, rather than apoptosis.[3][4]

ABTL0812 activates the PPAR receptors, inducing TRIB3 over-expression. TRIB3 binds to the Akt oncogene and inhibits the Akt/mTOR axis.[3]

Clinical trials

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ABTL0812 showed efficacy in Phase I clinical trials in patients with advanced cancer, with low toxicity and high tolerability.[3]

References

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  1. ^ a b c "Ability Pharmaceuticals Announces Orphan Drug Designation in the US for ABTL0812 in Pancreatic Cancer". Ability Pharmaceuticals SL.
  2. ^ "Ability Pharmaceuticals Announces Positive Phase 1 1b Study Results Of ABTL0812 In Cancer Patients With Advanced Solid Tumors". www.biospace.com.
  3. ^ a b c "New mechanism of antitumor action identified". Medical Xpress. 25 January 2016.
  4. ^ Erazo T, Lorente M, López-Plana A, Muñoz-Guardiola P, Fernández-Nogueira P, García-Martínez JA, et al. (May 2016). "The New Antitumor Drug ABTL0812 Inhibits the Akt/mTORC1 Axis by Upregulating Tribbles-3 Pseudokinase". Clinical Cancer Research. 22 (10): 2508–19. doi:10.1158/1078-0432.ccr-15-1808. hdl:2445/207600. PMID 26671995.