Referencia número: HY-13955

Telmisartan

(Synonyms: BIBR 277)

17 Cited Publications

Revisión del cliente

Based on 17 publication(s) in Google Scholar

Telmisartan is a potent, long lasting antagonist of angiotensin II type 1 receptor (AT1), selectively inhibiting the binding of ¹²⁵I-AngII to AT1 receptors with IC₅₀ of 9.2 nM.

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Pureza: 99.79%
No. CAS: 144701-48-4
Fòrmula: C₃₃H₃₀N₄O₂
Peso molecular:514.62

Almacenamiento:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 1 year , -20°C, 6 months

Telmisartan Chemical Structure

No. CAS: 144701-48-4

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Actividad biológica
- Descripciòn
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Ensayo clínico
Chemical Information
Publications (17)
Solvente y solubilidad
- In Vitro
- In Vivo
Protocolo
Pureza y Documentación
Referencias
Help & FAQs
Classifications
Bioz

Actividad biológica

Descripciòn

Telmisartan is a potent, long lasting antagonist of angiotensin II type 1 receptor (AT1), selectively inhibiting the binding of ¹²⁵I-AngII to AT1 receptors with IC₅₀ of 9.2 nM.

IC₅₀ & Target

AT1 Receptor

Ver todos los productos específicos de isoformas Angiotensin Receptor :

Cellular Effect

Cell Line	Type	Value	Description	References
CHO	EC₅₀	3.4 μM Compound: Telmisartan	Activation of Gal4-tagged human PPARgamma expressed in CHO cells by luciferase reporter gene assay Activation of Gal4-tagged human PPARgamma expressed in CHO cells by luciferase reporter gene assay	[PMID: 20656494]
CHO	IC₅₀	0.002 μM Compound: Telmisartan	Antagonist activity at human AT1 receptor expressed in CHO cells measured after overnight incubation by luciferase reporter gene assay Antagonist activity at human AT1 receptor expressed in CHO cells measured after overnight incubation by luciferase reporter gene assay	[PMID: 24462665]
COS-7	EC₅₀	4.7 μM Compound: Telmisartan	Transactivation of GAL4-fused human PPARgamma ligand binding domain expressed in African green monkey COS7 cells after 42 hrs by dual luciferase reporter gene assay Transactivation of GAL4-fused human PPARgamma ligand binding domain expressed in African green monkey COS7 cells after 42 hrs by dual luciferase reporter gene assay	[PMID: 27560282]
COS-7	EC₅₀	4.71 μM Compound: Telmisartan	Transactivation at Gal4 fused PPARgamma LBD (unknown origin) expressed in African green monkey COS7 cells after 42 hrs by luciferase assay Transactivation at Gal4 fused PPARgamma LBD (unknown origin) expressed in African green monkey COS7 cells after 42 hrs by luciferase assay	[PMID: 27569195]
CV-1	EC₅₀	>10 μM Compound: 1	Agonist activity at human PPARalpha expressed in african green monkey CV1 cells by Gal4 transactivation assay Agonist activity at human PPARalpha expressed in african green monkey CV1 cells by Gal4 transactivation assay	[PMID: 20079636]
CV-1	EC₅₀	>10 μM Compound: 1	Agonist activity at human PPARdelta expressed in african green monkey CV1 cells by Gal4 transactivation assay Agonist activity at human PPARdelta expressed in african green monkey CV1 cells by Gal4 transactivation assay	[PMID: 20079636]
CV-1	EC₅₀	>10 μM Compound: 1	Agonist activity at mouse PPARalpha expressed in african green monkey CV1 cells by Gal4 transactivation assay Agonist activity at mouse PPARalpha expressed in african green monkey CV1 cells by Gal4 transactivation assay	[PMID: 20079636]
CV-1	EC₅₀	>10 μM Compound: 1	Agonist activity at mouse PPARdelta expressed in african green monkey CV1 cells by Gal4 transactivation assay Agonist activity at mouse PPARdelta expressed in african green monkey CV1 cells by Gal4 transactivation assay	[PMID: 20079636]
CV-1	EC₅₀	2.02 μM Compound: 1	Agonist activity at human PPARgamma expressed in african green monkey CV1 cells by Gal4 transactivation assay Agonist activity at human PPARgamma expressed in african green monkey CV1 cells by Gal4 transactivation assay	[PMID: 20079636]
CV-1	EC₅₀	2.02 μM Compound: Telmisartan	Agonist activity at human PPARgamma expressed in CV-1 cells by reporter gene assay Agonist activity at human PPARgamma expressed in CV-1 cells by reporter gene assay	[PMID: 24462665]
CV-1	EC₅₀	4.06 μM Compound: 1	Agonist activity at mouse PPARgamma expressed in african green monkey CV1 cells by Gal4 transactivation assay Agonist activity at mouse PPARgamma expressed in african green monkey CV1 cells by Gal4 transactivation assay	[PMID: 20079636]
CV-1	EC₅₀	4.5 μM Compound: telmisartan	Activity at full length human PPARgamma transfected in CV1 cells assessed as transactivation activity after 24 hrs by PPRE-TK- luciferase reporter gene assay Activity at full length human PPARgamma transfected in CV1 cells assessed as transactivation activity after 24 hrs by PPRE-TK- luciferase reporter gene assay	[PMID: 25734377]
HEK293	IC₅₀	17.9 μM Compound: telmisartan	Inhibition of human MATE1-mediated ASP+ uptake expressed in HEK293 cells after 1.5 mins by fluorescence assay Inhibition of human MATE1-mediated ASP+ uptake expressed in HEK293 cells after 1.5 mins by fluorescence assay	[PMID: 23241029]
HepG2	IC₅₀	>10 μM Compound: 92124871	HARVARD: Cytotoxicity in HepG2 cell line HARVARD: Cytotoxicity in HepG2 cell line	[PMID: 22586124]
HepG2	IC₅₀	0.025 μM Compound: 92124871	HARVARD: Inhibition of liver stage Plasmodium berghei infection in HepG2 cells HARVARD: Inhibition of liver stage Plasmodium berghei infection in HepG2 cells	[PMID: 22586124]
Mesenchymal stem cells	EC₅₀	4.7 μM Compound: Tel	Induction of adiponectin secretion in human BMMSC cells in presence of IDX induction medium by ELISA assay Induction of adiponectin secretion in human BMMSC cells in presence of IDX induction medium by ELISA assay	[PMID: 37077388]

In Vitro

In intact RVSMC cells and in membrane preparations, telmisartan inhibits the binding of ¹²⁵I-AngII to AT1 receptors in a concentration-dependent manner, with an IC₅₀ of 9.2 ± 0.8 nM. In the same experimental conditions, angiotensin II displaces ¹²⁵I-AngII with an IC₅₀ value of 2.9 ± 0.5 nM. The specific binding of [³H]telmisartan to SMC membranes is displaced by unlabeled telmisartan with an IC₅₀ of 7.7 ± 1.8 nM and by cold AngII with an IC₅₀ of 32.7 ± 5.7 nM ^[1]. Telmisartan treatment (100 μM) reduces the proliferation of three EAC cell lines (OE19, OE33, and SKGT-4), induces cell cycle arrest in G0/G1 phase and regulates cell cycle-related proteins in EAC cells, and induces the phosphorylation of AMPK and regulates cell cycle-related proteins via the AMPK/mTOR pathway in EAC cells. Telmisartan inhibits the activation of RTKs, downstream effectors and cell cycle-related proteins^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

In the telmisartan (0.1, 0.3, and 1 mg/kg)-treated rats, the specific binding of [³H]telmisartan to the surface of living RVSMC is saturable and increases quickly to reach equilibrium within 1 h. Telmisartan dissociates very slowly from the receptor with a dissociation half-life (t1/2) of 75 min, which is comparable with candesartan and almost 5 times slower than angiotensin II (AngII). In vivo, telmisartan blunts the blood pressure response to exogenous AngII dose dependently^[1]. Telmisartan (10 mg/kg/d) administration effectively suppresses aneurysm pathogenesis after PPE infusion as well, regardless of whether treatment is initiated before or after aneurysm creation or continues for a limited or extended time. Telmisartan treatment is associated with reduced messenger RNA levels for CCL5 and matrix metalloproteinases 2 and 9 in aneurysmal aortae, with no apparent effect on PPARγ-regulated gene expression^[2]. Telmisartan (1 mg/kg/day) significantly ameliorates neuronal loss and the spatial acquisition impairment in 5XFAD mice, but without any changes of NeuN expression in the hippocampus layer. Telmisartan (1 mg/kg/day) treatment reduces amyloid burden and microglial accumulation in 5XFAD mice brain, induces microglial polarization towards neuroprotective phenotype, but does not alter the expression levels of NEP and IDE in 5XFAD mice specific brain areas^[3]. Telmisartan (0.05, 0.1, 1 mg/kg, p.o.) shows significant reduction in immobility time, antagonizes depression and anxiety, and also significantly attenuates serum cortisol, NO, IL-6 and IL-1β in rats^[4]. Telmisartan (50 μg, i.p.) leads to a 73.2% reduction in tumor growth in mice bearing xenografts derived from OE19 cells. Furthermore, miRNA expression is significantly altered by telmisartan in vivo^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Ensayo clínico

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

No. CAS 144701-48-4
Appearance Solid
Peso molecular 514.62
Fòrmula C₃₃H₃₀N₄O₂
Color White to off-white
SMILES

O=C(C1=CC=CC=C1C2=CC=C(CN3C4=CC(C5=NC6=CC=CC=C6N5C)=CC(C)=C4N=C3CCC)C=C2)O
Synonyms

BIBR 277
Envío

Room temperature in continental US; may vary elsewhere.

Almacenamiento

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	1 year
	-20°C	6 months

Publications (17)

All WBCell Proliferation/Viability AssayCell Migration/Invasion Assay

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Journal Impact Factor

J Immunother Cancer

Telmisartan increases olaparib efficacy in homologous recombination proficient tumors by augmenting type I interferon production. [Abstract]

2026 Mar 25;14(3):e012426. PMID: 41881499
J Pharm Anal

Prioritization of potential drug targets for diabetic kidney disease using integrative omics data mining and causal inference. [Abstract]

2025 Aug;15(8):101265. PMID: 40979545

Telmisartan purchased from MedChemExpress. Usage Cited in: J Pharm Anal. 2025 Aug;15(8):101265. [Abstract]

Telmisartan (4 and 40 mg/mL; 48 h) significantly suppressed the IGFBP4 and NLRP3-caspase-1 axis.
Pharmaceuticals (Basel)

The Discovery of Novel Agents against Staphylococcus aureus by Targeting Sortase A: A Combination of Virtual Screening and Experimental Validation. [Abstract]

2023 Dec 29;17(1):0. PMID: 38256891

Telmisartan purchased from MedChemExpress. Usage Cited in: Pharmaceuticals (Basel). 2023 Dec 29;17(1):0. [Abstract]

Toxicity assay suggests that Telmisartan (0.1-100 µM) has minimal toxicity at recommended clinical dosages.

Telmisartan purchased from MedChemExpress. Usage Cited in: Pharmaceuticals (Basel). 2023 Dec 29;17(1):0. [Abstract]

Even a lower concentration of 1 μM Telmisartan (1-10 μM ) substantially inhibited adhesion efficiency for the RN4220 strain.

Telmisartan purchased from MedChemExpress. Usage Cited in: Pharmaceuticals (Basel). 2023 Dec 29;17(1):0. [Abstract]

The effect of serial concentrations of Telmisartan (0.02-4000 μM) on the growth of S.aureus.
Int Immunopharmacol

Repurposing Azilsartan medoxomil attenuates periodontitis by targeting SERPINB9 to promote apoptosis of IL1B+ macrophages. [Abstract]

2026 May 15:177:116523. PMID: 41864017
Int Immunopharmacol

Telmisartan inhibits microglia-induced neurotoxic A1 astrocyte conversion via PPARγ-mediated NF-κB/p65 degradation. [Abstract]

2023 Oct:123:110761. PMID: 37544025
Biomolecules

Structure-Based Virtual Screening and Functional Validation of Potential Hit Molecules Targeting the SARS-CoV-2 Main Protease. [Abstract]

2022 Nov 25;12(12):1754. PMID: 36551182
Int J Obes

Depot-specific UCP1 expression in human white adipose tissue and its association with obesity-related markers. [Abstract]

2020 Mar;44(3):697-706. PMID: 31965068
J Cell Mol Med

Telmisartan anti-cancer activities mechanism through targeting N-cadherin by mimicking ADH-1 function. [Abstract]

2022 Apr;26(8):2392-2403. PMID: 35224849
Biosci Rep

Anti-tumoral potential of MDA19 in human osteosarcoma via suppressing PI3K/Akt/mTOR signaling pathway. [Abstract]

2018 Dec 14;38(6):BSR20181501. PMID: 30442873
Saudi Pharm J

Study of influence of Catha edulis (Khat) chewing on oral pharmacokinetics of irbesartan in rats using a newly developed HPLC-UV method. [Abstract]

2022 Mar;30(3):237-244. PMID: 35498225
Open Life Sci

Telmisartan Induces Osteosarcoma Cells Growth Inhibition and Apoptosis Via Suppressing mTOR Pathway. [Abstract]

2018 Jul 5:13:242-249. PMID: 33817089

Telmisartan purchased from MedChemExpress. Usage Cited in: Open Life Sci. 2018 Jul 5:13:242-249. [Abstract]

Expression of the apoptosis-related proteins including Bax, Bcl-2 and Cleaved Caspase-3 treated with Telmisartan in OS cells are determined by western blot analysis.
Oncol Lett

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway. [Abstract]

2018 Apr;15(4):5859-5864. PMID: 29552215

Telmisartan purchased from MedChemExpress. Usage Cited in: Oncol Lett. 2018 Apr;15(4):5859-5864. [Abstract]

Western blot analysis of A549 cells treated with Telmisartan for 24 h. The band intensities are quantified. The results are normalized to the GAPDH loading control.
Mol Biol Res Commun

Combinatorial effects of telmisartan and docetaxel on cell viability and metastatic gene expression in human prostate and breast cancer cells. [Abstract]

2022 Mar;11(1):11-20. PMID: 35463822
Patent

US20230147853A1.
Research Square Preprint

2023 Apr 20.
bioRxiv

2023 Mar 12.
Oxid Med Cell Longev

Effects of the (Pro)renin Receptor on Cardiac Remodeling and Function in a Rat Alcoholic Cardiomyopathy Model via the PRR-ERK1/2-NOX4 Pathway. [Abstract]

2019 Mar 13:2019:4546975. PMID: 31049135

Solvente y solubilidad

In Vitro:

DMSO : 6.67 mg/mL (12.96 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.9432 mL

9.7159 mL

19.4318 mL

5 mM

0.3886 mL

1.9432 mL

3.8864 mL

10 mM

0.1943 mL

0.9716 mL

1.9432 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Calculadora de molaridad

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Calculadora de dilución

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 0.67 mg/mL (1.30 mM); Clear solution

This protocol yields a clear solution of ≥ 0.67 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (6.7 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 0.67 mg/mL (1.30 mM); Clear solution

This protocol yields a clear solution of ≥ 0.67 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (6.7 mg/mL) to 900 μL Corn oil, and mix evenly.

Working Solution

For the following dissolution methods, please prepare the working solution directly:

It is recommended to prepare fresh solutions and use them promptly within a short period of time.

The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 0.5% CMC-Na/saline water

Solubility: 3 mg/mL (5.83 mM); Suspended solution; Need ultrasonic

Protocol 2

Add each solvent one by one: 17% Solutol HS-15 in Saline

Solubility: 3.33 mg/mL (6.47 mM); Suspended solution; Need ultrasonic and warming

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Protocolo

Cell Assay^[5]

Cell proliferation is assayed using the CCK-8 cell counting kit. Briefly, 5×10³ cells are seeded into each well of a 96-well plate and cultured in 100 μL of RPMI-1640 supplemented with 10% FBS. After 24 h, ARBs (telmisartan, irbesartan, losartan, and valsartan at 0, 1, 10, or 100 μM) or vehicle is added to each well, and cells are cultured for an additional 48 h. CCK-8 reagent (10 μL) is added to each well, and the plates are incubated at 37°C for 3 h. The absorbance is measured at 450 nm using a microplate reader.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration^[5]

Male athymic mice (BALB/c-nu/nu; 6 weeks old; 20-25 g) are maintained under specific pathogen-free conditions using a laminar airflow rack. The mice have continuous free access to sterilized (γ-irradiated) food and autoclaved water. Each mouse is subcutaneously inoculated with OE19 cells (5×10⁶ cells per animal) in the flank. One week later, the xenografts are identifiable as masses with a maximal diameter > 4 mm. The animals are randomly assigned to treatment with telmisartan (50 μg per day) or diluent only (control). The telmisartan group is intraperitoneally (i.p.) injected five times per week with 2 mg/kg telmisartan for four weeks; the control group is administered 5% DMSO alone for four weeks. Tumor growth is monitored daily by the same investigators, and tumor size is measured weekly. The tumor volume (mm³) is calculated as the tumor length (mm) × tumor width (mm)²/2. All animals are sacrificed on day 22 after treatment, and all animals survive during this period. Between-group differences in tumor growth are analyzed by two-way ANOVA.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Pureza y Documentación

Select Batch:

Pureza: 99.98%

Assay: 99.98%

ee.: 99.98%

Ficha de datos (283 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Instrucciones de manejo (2659 KB)

Referencias

[1]. Maillard MP, et al. In vitro and in vivo characterization of the activity of telmisartan: an insurmountable angiotensin II receptor antagonist. J Pharmacol Exp Ther. 2002 Sep;302(3):1089-95. [Content Brief]

[2]. Xuan H, et al. Inhibition or deletion of angiotensin II type 1 receptor suppresses elastase-induced experimental abdominal aortic aneurysms. J Vasc Surg. 2017 Apr 20. pii: S0741-5214(17)30100-3. [Content Brief]

[3]. Torika N, et al. Intranasal telmisartan ameliorates brain pathology in five familial Alzheimer's disease mice. Brain Behav Immun. 2017 Apr 3. [Content Brief]

[4]. Aswar U, et al. Telmisartan attenuates diabetes induced depression in rats. Pharmacol Rep. 2017 Apr;69(2):358-364. [Content Brief]

[5]. Fujihara S, et al. The angiotensin II type 1 receptor antagonist telmisartan inhibits cell proliferation and tumor growth of esophageal adenocarcinoma via the AMPKα/mTOR pathway in vitro and in vivo. Oncotarget. 2017 Jan 31;8(5):8536-8549. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	1.9432 mL	9.7159 mL	19.4318 mL	48.5795 mL
	5 mM	0.3886 mL	1.9432 mL	3.8864 mL	9.7159 mL
	10 mM	0.1943 mL	0.9716 mL	1.9432 mL	4.8580 mL

Keywords

Telmisartan

17 Cited Publications

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Telmisartan

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Publications Citing Use of MedChemExpress (MCE) Telmisartan

Ver todos los productos específicos de isoformas Angiotensin Receptor

Actividad biológica

Chemical Information

Publications (17)

Solvente y solubilidad

Protocolo

Pureza y Documentación

Referencias

Help & FAQs

Complete Stock Solution Preparation Table

Telmisartan Related Classifications

HY-13955 Related Classifications