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Chemical Structure| 103890-78-4 Chemical Structure| 103890-78-4

Structure of Lacidipine
CAS No.: 103890-78-4

Chemical Structure| 103890-78-4

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Lacidipine is a L-type calcium channel blocker, used for treating high blood pressure.

Synonyms: GX 1048; GR-43659X; Motens

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Product Citations

Product Citations

Sejal Sharma ; Liping Feng ; Nicha Boonpattrawong ; Arvinder Kapur ; Lisa Barroilhet ; Manish Patankar , et al.

Abstract: Focused screening on target-prioritized compound sets can be an efficient alternative to high throughput screening (HTS). For most biomolecular targets, compound prioritization models depend on prior screening data or a target structure. For phenotypic or multi-protein pathway targets, it may not be clear which public assay records provide relevant data. The question also arises as to whether data collected from disparate assays might be usefully consolidated. Here, we report on the development and application of a data mining pipeline to examine these issues. To illustrate, we focus on identifying inhibitors of oxidative phosphorylation, a druggable metabolic process in epithelial ovarian tumors. The pipeline compiled 8415 available OXPHOS-related bioassays in the PubChem data repository involving 312,093 unique compound records. Application of PubChem assay activity annotations, PAINS, and Lipinski-like bioavailability filters yields 1,852 putative OXPHOS-active compounds that fall into 464 clusters. These chemotypes are diverse but have relatively high hydrophobicity and molecular weight but lower complexity and drug-likeness. These chemotypes show a high abundance of bicyclic ring systems and oxygen containing functional groups including ketones, allylic oxides (alpha/beta unsaturated carbonyls), hydroxyl groups, and ethers. In contrast, amide and primary amine functional groups have a notably lower than random prevalence. UMAP representation of the chemical space shows strong divergence in the regions occupied by OXPHOS-inactive and -active compounds. Of six compounds selected for experimental validation, 4 showed statistically significant inhibition of electron transport in bioenergetics assays. Two of these four compounds, lacidipine and esbiothrin, increased in intracellular oxygen radicals (a major hallmark of most OXPHOS inhibitors) and decreased the viability of two ovarian cancer cell lines, ID8 and OVCAR5. Finally, data from the pipeline were used to train random forest and support vector classifiers that effectively prioritized OXPHOS inhibitory compounds within a held-out test set (ROCAUC 0.962 and 0.927, respectively) and on another set containing 44 documented OXPHOS inhibitors outside of the training set (ROCAUC 0.900 and 0.823). This prototype pipeline is extensible and could be adapted for focus screening on other phenotypic targets for which sufficient public data are available.

Keywords: Data mining ; PubChem ; Oxidative Phosphorylation ; Electron Transport Chain ; Ovarian Cancer ; Cheminformatics ; Bioenergetics assays ; Cancer therapeutics

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Product Details of Lacidipine

CAS No. :103890-78-4
Formula : C26H33NO6
M.W : 455.54
SMILES Code : O=C(C1=C(C)NC(C)=C(C(OCC)=O)C1C2=CC=CC=C2/C=C/C(OC(C)(C)C)=O)OCC
Synonyms :
GX 1048; GR-43659X; Motens
MDL No. :MFCD00865936
InChI Key :GKQPCPXONLDCMU-CCEZHUSRSA-N
Pubchem ID :5311217

Safety of Lacidipine

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • Calcium Channel

In Vitro:

Cell Line
Concentration Treated Time Description References
guinea-pig ventricular myocytes 0.1 mM 2 minutes To investigate the inhibitory effect of Lacidipine on L-type calcium current, results showed that 0.1 mM Lacidipine reduced L-type calcium current to 66±4% of control value within 2 minutes without altering the current-voltage relationship. Br J Pharmacol. 1997 Feb;120(4):667-75
HEK293A cells 10 ×10−6, 20×10−6, and 40×10−6 Μ 6 hours Inhibit IDO1/2 enzymatic activity Adv Sci (Weinh). 2025 Jan;12(3):e2409310
MDA-MB-231 cells 10 ×10−6, 20×10−6, and 40×10−6 m 24 hours Reduce the expression of IDO1, IDO2, and TDO2 Adv Sci (Weinh). 2025 Jan;12(3):e2409310
HeLa cells 5 ×10−6, 10×10−6, 20×10−6, 40×10−6, and 80×10−6 m 24 hours Inhibit IFN γ-induced Kyn production Adv Sci (Weinh). 2025 Jan;12(3):e2409310
murine aortic smooth muscle cells 30 μM 1-hour pretreatment followed by 4h and 24h To investigate the effect of Lacidipine on ELDL-induced foam cell formation in smooth muscle cells. Results showed that Lacidipine significantly inhibited ELDL-mediated foam cell formation. Arterioscler Thromb Vasc Biol. 2016 Jun;36(6):1101-13
OVCAR5 10 μM 72 h Assess cell viability and cell death, results showed lacidipine significantly reduced viability and induced cell death in OVCAR-5 cells J Cheminform. 2024 Oct 7;16(1):112
ID8 10–40 μM 45 min Measure oxygen consumption rate (OCR) and ATP production, results showed lacidipine significantly inhibited OCR and ATP production in ID8 cells in a dose-dependent manner J Cheminform. 2024 Oct 7;16(1):112
Mouse peritoneal macrophages 1-20 μM 2-24 hours To evaluate the inhibitory effect of Lacidipine on cholesterol esterification. Results showed that Lacidipine significantly inhibited cholesterol esterification at concentrations of 10 μM and 20 μM, reducing it to 30% and 24% of the control value, respectively. Br J Pharmacol. 1997 Nov;122(6):1209-15
rat aortic smooth muscle cells 80pM-640pM 90 minutes Investigation of Lacidipine's inhibitory effect on K+-induced contraction in rat aorta, with steady-state IC50 of 160pM Br J Pharmacol. 1993 May;109(1):100-6

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
BALB/c mice 4T1-Luc breast cancer model Oral 0.5 mg/kg, 1 mg/kg, 10 mg/kg, 20 mg/kg Every 2 days for 21 days Enhance the anti-tumor effect of chemotherapeutic agents Adv Sci (Weinh). 2025 Jan;12(3):e2409310
New Zealand male rabbits Hypercholesterolemic diet-induced atherosclerosis model Oral 1, 3, 10 mg/kg/day Once daily for two months To evaluate the effect of Lacidipine on cholesterol esterification in the aortic arch. Results showed that Lacidipine reduced cholesterol esterification in a dose-dependent manner, with inhibition rates of 24%, 30%, and 41% at doses of 1, 3, and 10 mg/kg/day, respectively. Additionally, drug treatment reduced the total cholesterol content in the vessel wall. Br J Pharmacol. 1997 Nov;122(6):1209-15
Rat Rat aortic rings In vitro organ bath 80pM-640pM Single administration, monitored for up to 120 minutes Evaluation of Lacidipine's inhibitory effect on vascular contraction under depolarizing conditions, showing slow and prolonged action Br J Pharmacol. 1993 May;109(1):100-6
New Zealand White rabbits Atherosclerotic model induced by cholesterol-rich diet Oral (mixed with food) 1, 3, and 10 mg/kg/day Once daily for 8 weeks To investigate the effect of Lacidipine on atherosclerotic lesions induced by cholesterol-rich diet. Results showed that Lacidipine significantly reduced the extent of aortic fatty lesions (by 40%) at the dose of 10 mg kg-1 day-1 and dose-dependently inhibited carotid intimal hyperplasia (I/M ratios were 0.47±0.02, 0.40±0.09, and 0.32±0.02 for doses 1, 3, and 10 mg kg-1 day-1, respectively). Br J Pharmacol. 1996 May;118(2):215-9
Salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP) Salt-loaded SHRSP model Oral (via supplemented chow) 0.3, 1, or 3 mg/kg/day Once daily for 6 weeks (from 8 to 14 weeks of age) Investigated the protective effects of Lacidipine on cardiac remodeling and renin production in salt-loaded SHRSP. The lowest dose (0.3 mg/kg) restored physiological downregulation of renin by high salt, reduced left ventricular hypertrophy, and decreased mRNA levels of atrial natriuretic factor and TGF-β1. Intermediate doses reduced blood pressure and PRA, but the highest dose (3 mg/kg) increased kidney renin mRNA. Br J Pharmacol. 2001 Dec;134(7):1516-22
Stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY) Salt-loaded stroke-prone spontaneously hypertensive rats (SL-SHRSP) and control (NS-SHRSP) Oral 0.3 mg/kg/day and 1 mg/kg/day Once daily for 6 weeks To investigate the effect of lacidipine on cardiac hypertrophy and endothelin-1 (ET-1) gene expression. The results showed that lacidipine dose-dependently inhibited ventricle hypertrophy and ET-1 gene overexpression in SL-SHRSP, and this effect was unrelated to changes in systolic blood pressure (SBP). Br J Pharmacol. 1996 Jun;118(3):659-64
Beagle dogs Healthy beagle dogs Oral 4 mg Single dose To evaluate the bioequivalence of three lacidipine formulations in beagle dogs. Results showed that the Cmax and AUC of the three formulations did not meet the bioequivalence criteria in 6 beagle dogs, but achieved bioequivalence in virtual simulations with 24 beagle dogs. Asian J Pharm Sci. 2017 Jan;12(1):98-104

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT01587742 - Completed - -
NCT00460915 Hypertension Phase 4 Completed - Korea, Republic of ... More >> Korea University Guro Hospital Seoul, Korea, Republic of, 152-703 Less <<
NCT02218684 Healthy Phase 1 Completed - -
NCT02240641 - Terminated - -
NCT02232607 Angina Pectoris Phase 2 Completed - -
NCT00533858 Hypertension Phase 4 Unknown September 2008 Korea, Republic of ... More >> Seoul National University Bundang Hospital Recruiting Seongnam, Kyeonggi, Korea, Republic of, 463-707 Contact: Cheol-Ho Kim, MD, PhD    82-31-787-7001    cheolkim@snu.ac.kr Less <<
NCT02235402 Hypertension Phase 4 Completed - -
NCT02264158 Healthy Phase 1 Completed - -
NCT02203500 Healthy Phase 1 Completed - -
NCT02209649 Healthy Phase 1 Completed - -
NCT02235415 - Completed - -
NCT00338338 Uncomplicated Hypertension ... More >> Hypertension Essential Less << Phase 4 Completed - Taiwan ... More >> GSK Investigational Site Taipei, Taiwan, 100 Less <<
NCT00328965 Diabetes Mellitus, Type 2|Esse... More >>ntial Hypertension Less << PHASE4 COMPLETED 2025-05-06 -
NCT02177331 Hypertension PHASE3 COMPLETED - -

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.20mL

0.44mL

0.22mL

10.98mL

2.20mL

1.10mL

21.95mL

4.39mL

2.20mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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