Details
Stereochemistry | MIXED |
Molecular Formula | C13H20N2O4 |
Molecular Weight | 268.3089 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 2 / 4 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1CCN(CC1)C(=O)C2[C@@H]3CC[C@@H](O3)C2C(O)=O
InChI
InChIKey=JUQMLSGOTNKJKI-IZUQBHJASA-N
InChI=1S/C13H20N2O4/c1-14-4-6-15(7-5-14)12(16)10-8-2-3-9(19-8)11(10)13(17)18/h8-11H,2-7H2,1H3,(H,17,18)/t8-,9+,10?,11?/m0/s1
Molecular Formula | C13H20N2O4 |
Molecular Weight | 268.3089 |
Charge | 0 |
Count |
|
Stereochemistry | MIXED |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 4 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
3-[(4-Methyl-1-piperazinyl)carbonyl]-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid (LB-100) is an experimental cancer therapeutic with cytotoxic activity against cancer cells in culture and antitumor activity in animals. It is an intravenously administered, small-molecule, serine-threonine protein phosphatase (PP2A) inhibitor, being developed by Lixte Biotechnology Holdings. LB-100 delivers an active metabolite into the cell, potently inhibiting specifically the s/t ptases PP2A. Inhibition of PP2A markedly potentiates the effectiveness of standard anti-cancer drugs and X-ray that exert their clinical benefit by damaging DNA thereby inhibiting faithful cell division. Although the growth of normal cells including those of the bone marrow, GI tract, and hair is also impaired by cytotoxic cancer treatment, cancer cells often have acquired genetic damage that permits their unrestrained growth but also reduces their ability to repair DNA damage. Inhibition of PP2A by LB-100 further impairs DNA repair to a greater extent in the cancer cell than in the normal cell providing more selective killing. LB-100 used alone has modest inhibitory activity against many cancers in model systems, but certain human cancers, possessing unique genetic changes in addition to those reducing DNA damage repair, are particularly vulnerable to inhibition of PP2A by LB-100. Among these is myelodysplastic syndrome (MDS), an increasingly common neoplastic disease, especially in persons aged 65 and older, characterized by failure of the bone marrow. In particular, a variant of MDS termed del(5q)MDS is missing ~50% of its PP2A activity rendering this tumor potentially vulnerable to further pharmacologic inhibition of PP2A
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL4703 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25304380 |
0.85 µM [IC50] | ||
Target ID: P67775 Gene ID: 5515.0 Gene Symbol: PPP2CA Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/25376608 |
1.4 µM [IC50] |
PubMed
Title | Date | PubMed |
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Inhibition of protein phosphatase 2A sensitizes pancreatic cancer to chemotherapy by increasing drug perfusion via HIF-1α-VEGF mediated angiogenesis. | 2014 Dec 28 |
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Safety, Tolerability, and Preliminary Activity of LB-100, an Inhibitor of Protein Phosphatase 2A, in Patients with Relapsed Solid Tumors: An Open-Label, Dose Escalation, First-in-Human, Phase I Trial. | 2017 Jul 1 |
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The Antitumor Drug LB-100 Is a Catalytic Inhibitor of Protein Phosphatase 2A (PPP2CA) and 5 (PPP5C) Coordinating with the Active-Site Catalytic Metals in PPP5C. | 2019 Mar |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28039265
Solid tumors:The recommended phase II dose of LB-100 is 2.33 mg/m2 daily for 3 days every 3 weeks
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25304380
LB-100 inhibits the cell growth with IC50 of 2.3 uM (in BxPc-3) or 1.7 μM (in Panc-1 cell).
Substance Class |
Chemical
Created
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Record UNII |
0C1JUU9S0L
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C106430
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1632032-53-1
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DB15412
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LB-100
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admin on Sat Dec 16 11:32:56 GMT 2023 , Edited by admin on Sat Dec 16 11:32:56 GMT 2023
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PRIMARY | LB-100: Catalog No.S7537LB-100 is a water soluble protein phosphatase 2A (PP2A) inhibitor. In Phase 1. LB-100 inhibits the cell growth with IC50 of 2.3 .MU.M (in BxPc-3) or 1.7 .MU.M (in Panc-1 cell). In BxPc-3, Panc-1, and SW1990 cells, LB-100 reduces the PP2A activity by 30-50%. LB-100 increases concentration of doxorubicin within cells (2.5 fold to control) and sensitizes tumor cells to the cytotoxicity of doxorubicin. LB-100 increaseds VEGF secretion, and thus enhances HIF-1.ALPHA.-VEGF mediated angiogenesis.In vivo: In a mouse pancreatic cancer xenograft model, LB-100 (2 mg/kg, i.p.) enhances chemotherapy of doxorubicin. LB-100 causes higher density of microvessel in tumors and rapid blood flow at the surface of tumors. | ||
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ACTIVE MOIETY |
Originator: Lixte Biotechnology Holdings; Developer: INSERM, Lixte Biotechnology Holdings; Class: Antineoplastic, Small molecule; Mechanism of Action: Phosphoprotein phosphatase inhibitor, Protein phosphatase 2A inhibitor; Highest Development Phases: Phase I for Solid tumours, Preclinical for Depressive disorders, Haematological disorders, Research for Ischaemia; Most Recent Events: 08 Feb 2016 Lixte Biotechnology plans a proof-of-concept clinical study for Depressive disorders, 03 Feb 2016 Preclinical trials in Depressive disorders in France (unspecified route), 30 Dec 2015 LB 100 licensed to Taipei Medical University in Asia
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