MEDI3726
MEDI3726 (ADCT-401) is a prostate-specific membrane antigen (PSMA)-targeting antibody-drug conjugate (ADC), composed of LP Tesirine (HY-128952) and antibody J591 (HY-P991359). MEDI3726 binds PSMA’s extracellular domain, triggers endocytosis, undergoes lysosomal degradation to release a pyrrolobenzodiazepine warhead. MEDI3726 induces DNA crosslinking, DNA damage, cell death, cytotoxicity, and inhibits tumor growth in mouse xenograft models. MEDI3726 undergoes in vivo catabolism primarily via heavy-light chain dissociation, with minimal warhead deconjugation. MEDI3726 can be used for the research of metastatic castration-resistant prostate cancer and prostate cancers.
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- 순도&문서
- References
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Help & FAQs
Biological Activity
MEDI3726 (ADCT-401) exhibits potent, specific cytotoxicity in PSMA-expressing prostate cancer cell lines, with greatly reduced activity in PSMA-negative prostate cancer cell lines[3].
MEDI3726 (0.2 μg/mL; 1 h) cross-reacts with human and cynomolgus monkey soluble PSMA with similar potency, but does not cross-react with rat soluble PSMA[4].
MEDI3726 (up to 7 days) remains stable and active at 37°C in PBS, human plasma, or cynomolgus monkey plasma[4].
MEDI3726 (5-7 days) potently and specifically kills PSMA-positive human prostate cancer cell lines LNCaP (IC50 = 0.02 nM), LNCaP C4-2 (IC50 = 0.06 nM), MDA PCa 2b (IC50 = 0.002 nM), and CWR22Rv1 (IC50 = 0.29 nM), but shows no targeted cytotoxicity in PSMA-negative PC-3 (IC50 = 29.3 nM) and DU145 cell lines (IC50 = 44.9 nM)[4].
MEDI3726 (24 h) is specifically internalized and trafficked to lysosomes in PSMA-positive LNCaP cells, but not in PSMA-negative PC-3 cells[4].
MEDI3726 (6 nM; 2 h treatment) induces persistent DNA interstrand crosslinks in PSMA-positive LNCaP cells, but does not induce significant DNA crosslinking in PSMA-negative PC-3 cells[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MEDI3726 (0.33-1 mg/kg; i.v.; single dose) displays dose-dependent antitumor activity in mouseCWR22Rv1 castration-resistant prostate cancer xenografts[4].
MEDI3726 (0.33-1 mg/kg; i.v.; single dose) exhibits only limited antitumor activity in mouse PSMA-negative PC-3 prostate cancer xenografts at the 1 mg/kg single dose[4].
MEDI3726 (0.1-0.9 mg/kg; i.v.; once every 3 weeks; 3 doses) demonstrates dose-dependent, statistically significant antitumor activity in highly PSMA-positive LuCaP prostate cancer mosue PDX models[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:MF1 nude mice (male, 4-8 weeks old, 22.6-35.3 g) subcutaneously implanted with LNCaP human prostate cancer cells[4]
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Dosage:0.11; 0.33; 1 mg/kg
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Administration:i.v.; single dose
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Result:Showed dose-dependent antitumor activity.
Produced extended tumor stasis preceding regrowth with a single 1 mg/kg dose.
Increased time-to-endpoint survival significantly with a single 1 mg/kg dose compared with all other groups.
Associated with a statistically significant increase in animal survival at doses of 0.33 mg/kg and 1 mg/kg compared with the naked antibody group.
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Animal Model:C.B-17 SCID mice (male, 10 weeks old, 18.6-27.2 g) subcutaneously implanted with . CWR22Rv1 cells[4]
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Dosage:0.33; 1 mg/kg
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Administration:i.v.; single dose
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Result:Showed dose-dependent antitumor activity.
Induced prolonged tumor regression of approximately 50 days with a single 1 mg/kg dose.
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Animal Model:MF1 nude mcie (female, 11 weeks old, 17.5-27.6 g) subcutaneously implanted with PC-3 human prostate cancer tumor fragments[4]
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Dosage:0.33; 1 mg/kg
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Administration:i.v.; single dose
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Result:Showed limited antitumor activity at the highest tested dose of 1 mg/kg.
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Animal Model:C.B-17/IcrHsd-Prkdcscid mice (male, 8-12 weeks old, 21.1-25.5 g) subcutaneously implanted with LuCaP human prostate cancer tumor fragments[4]
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Dosage:0.1; 0.3; 0.9 mg/kg
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Administration:i.v.; once every 3 weeks; 3 doses
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Result:Showed dose-dependent antitumor activity.
Produced statistically significant responses.
Produced statistically significant tumor regression.
Chemical Information
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SMILES
[MEDI3726]
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Synonyms
ADCT-401
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
[1]. de Bono JS, et al. Phase I Study of MEDI3726: A Prostate-Specific Membrane Antigen-Targeted Antibody-Drug Conjugate, in Patients with mCRPC after Failure of Abiraterone or Enzalutamide. Clin Cancer Res. 2021;27(13):3602-3609. [Content Brief]
[2]. Huang Y, et al. Multifaceted Bioanalytical Methods for the Comprehensive Pharmacokinetic and Catabolic Assessment of MEDI3726, an Anti-Prostate-Specific Membrane Antigen Pyrrolobenzodiazepine Antibody-Drug Conjugate. Anal Chem. 2020;92(16):11135-11144. [Content Brief]
[4]. Cho S, et al. Antitumor Activity of MEDI3726 (ADCT-401), a Pyrrolobenzodiazepine Antibody-Drug Conjugate Targeting PSMA, in Preclinical Models of Prostate Cancer. Mol Cancer Ther. 2018;17(10):2176-2186. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MEDI3726 Related Classifications
HY-185729 Related Classifications
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- MEDI3726
- ADCT-401
- MEDI 3726
- MEDI-3726
- ADCT401
- ADCT 401
- Antibody-Drug Conjugates (ADCs)
- PSMA
- lysosomal degradation
- metastatic castration-resistant prostate cancer
- extracellular domain
- prostate-specific membrane antigen
- PSMA-positive cancer cells
- xenograft models
- endocytosis
- DNA crosslinking
- DNA damage
- pyrrolobenzodiazepine
- Inhibitor
- inhibitor
- inhibit