PSMA-Val-Cit-PAB-MMAE

Name: PSMA-Val-Cit-PAB-MMAE
Brand: MedChemExpress
SKU: HY-141860
Rating: 4.5 (0 reviews)

Cat. No.: HY-141860 Purity: 99.52%: Data Sheet
COA

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PSMA-Val-Cit-PAB-MMAE is a small-molecule conjugate targeting PSMA, with Monomethyl auristatin E (MMAE) (HY-15162) as its cytotoxic payload. PSMA-Val-Cit-PAB-MMAE binds to PSMA, thereby being delivered into PSMA-expressing prostate cancer cells. Subsequently, the Val-Cit linker is cleaved under the mediation of cathepsin B, releasing active MMAE. PSMA-Val-Cit-PAB-MMAE inhibits CYP3A4 activity (IC₅₀ = 11.2 μM), induces intracellular ROS production and oxidative stress, disrupts the cytoskeleton through microtubule destabilization, and induces prostate cancer cell death. PSMA-Val-Cit-PAB-MMAE can be used in research related to prostate cancer.

For research use only. We do not sell to patients.

PSMA-Val-Cit-PAB-MMAE Chemical Structure

CAS No. : 2748039-79-2

Size	Stock	Quantity
1 mg	In-stock	Estimated Time of Arrival: December 31
5 mg	In-stock	Estimated Time of Arrival: December 31
10 mg	In-stock	Estimated Time of Arrival: December 31
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100 mg	Get quote

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•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

View All Cytochrome P450 Isoform Specific Products:

View All Isoforms

CYP1 CYP2 CYP3 CYP4 CYP11 CYP17 Aromatase/CYP19A1 CYP26 CYP51 CYP1A2 CYP2D6 CYP2C9 CYP2C19 CYP3A CYP3A4 CYP17A1

Biological Activity
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target

Auristatin

Cellular Effect

Cell Line	Type	Value	Description	References
CWR22R	CC₅₀	29 nM Compound: PSMA-Val-Cit-PAB-MMAE	Cytotoxicity against human 22Rv1 cells expressing PMSA measured using MTT assay Cytotoxicity against human 22Rv1 cells expressing PMSA measured using MTT assay	[PMID: 34797052]
PC-3	CC₅₀	27 nM Compound: PSMA-Val-Cit-PAB-MMAE	Cytotoxicity against human PC-3 cells not expressing PMSA measured using MTT assay Cytotoxicity against human PC-3 cells not expressing PMSA measured using MTT assay	[PMID: 34797052]

In Vitro

PSMA-Val-Cit-PAB-MMAE exhibits nanomolar cytotoxicity in both PSMA-expressing 22Rv1 and PSMA-null PC-3 human prostate cancer cell lines, with CC₅₀ values of 29 nM and 27 nM, respectively^[1].
PSMA-Val-Cit-PAB-MMAE (27-29 nM; 1 h) induces significant oxidative stress in 22Rv1 and PC-3 human prostate cancer cells, increasing intracellular hydrogen peroxide levels to twice and three times the control levels, respectively, after 1 h incubation at its CC₅₀ concentration^[1].
PSMA-Val-Cit-PAB-MMAE (27-29 nM; up to 40 min) significantly reduces the stiffness of 22Rv1 human prostate cancer cells after incubation at its CC₅₀ concentration, but does not alter the stiffness of PC-3 human prostate cancer cells over 40 minutes^[1].
PSMA-Val-Cit-PAB-MMAE (40 μM; up to 8 h) is efficiently cleaved by recombinant cathepsin B in a pH-dependent manner, with the fastest hydrolysis at pH 3.6, but the highest release of free MMAE occurs at pH 5.6^[1].
PSMA-Val-Cit-PAB-MMAE (1-10000 μg/mL) does not induce gene mutations in Salmonella typhimurium strains TA98, TA97, or TA100 at concentrations up to 10000 μg/mL, with or without metabolic activation^[1].

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

In Vivo

PSMA-Val-Cit-PAB-MMAE (0.3 mg/kg; i.v.; three times at five-day intervals) exhibits potent antitumor activity against PSMA-positive 22Rv1 prostate cancer xenografts in nude mice, achieving 77.4−84.5% tumor growth inhibition^[1].
PSMA-Val-Cit-PAB-MMAE (0.3 mg/kg; i.v.; three times at five-day intervals) shows weak antitumor activity against low-PSMA PC-3 prostate cancer xenografts in nude mice, achieving a maximum 37.7% tumor growth inhibition^[1].
PSMA-Val-Cit-PAB-MMAE (0.3 mg/kg; i.p.; daily; 5 days) exhibits potent antitumor activity against PSMA-positive 22Rv1 prostate cancer xenografts in nude mice, achieving 70−85% tumor growth inhibition with 100% survival^[1].
PSMA-Val-Cit-PAB-MMAE (0.2-0.4 mg/kg; i.p.; daily; 5 days) inhibits tumor growth in DU145 prostate cancer xenografts in nude mice^[1].
PSMA-Val-Cit-PAB-MMAE (2-60 mg/kg; i.v.; single dose) has a median lethal dose of 6.3 mg/kg in healthy male ICR mice following a single intravenous injection, resulting in a therapeutic index of 21^[1].
PSMA-Val-Cit-PAB-MMAE (1-30 mg/kg; i.v.; single dose) has a median lethal dose of 4.9 mg/kg in healthy male Wistar rats following a single intravenous injection^[1].
PSMA-Val-Cit-PAB-MMAE (150-225 μg/kg; i.v.; once every three weeks; three months) exhibits moderate chronic toxicity in healthy male Wistar rats, with dose-dependent testicular pathology and transient gastrointestinal effects at the highest tested dose of 225 μg/kg, and no mortality observed^[1].
PSMA-Val-Cit-PAB-MMAE (81-122 μg/kg; i.v.; once every three weeks; three months) exhibits moderate chronic toxicity in healthy male Soviet Chinchilla rabbits, with one death in the highest dose group, immunological and pancreatic effects, and testicular pathology observed in some animals^[1].
PSMA-Val-Cit-PAB-MMAE (up to 14 mg/kg cumulative; i.v.; daily) does not exhibit significant cumulative toxicity in healthy male Wistar rats with daily repeated intravenous injections, as indicated by a cumulation index of 1.45, despite increased mortality with higher cumulative doses^[1].

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

Animal Model:	BALB/c nu/nu (male, 8−10 weeks old, 21−25 g, subcutaneous xenograft of 22Rv1 PSMA-positive human prostate carcinoma cells)^[1]
Dosage:	0.3 mg/kg
Administration:	i.v.; three times at five-day intervals
Result:	Achieved tumor growth inhibition (TGI) ranging from 77.4−84.5% relative to the control group. Had no effect on the general condition or body weight of the mice.

Animal Model:	BALB/c nu/nu (male, 8−10 weeks old, 21−25 g, subcutaneous xenograft of PC-3 low-PSMA human prostate adenocarcinoma cells)^[1]
Dosage:	0.3 mg/kg
Administration:	i.v.; three times at five-day intervals
Result:	Achieved tumor growth inhibition (TGI) not exceeding 37.7% relative to the control group. Had no effect on the general condition or body weight of the mice.

Animal Model:	Nude mice (male, subcutaneous xenograft of 22Rv1 PSMA-positive human prostate carcinoma cells)^[1]
Dosage:	0.3 mg/kg
Administration:	i.p.; daily; 5 days
Result:	Maintained 100% mice survival during the experiment. Achieved tumor growth inhibition (TGI) ranging from 70−85% relative to the control group.

Animal Model:	Nude mice (male, subcutaneous xenograft of DU145 human prostate cancer cells)^[1]
Dosage:	0.2 mg/kg; 0.4 mg/kg
Administration:	i.p.; daily; 5 days
Result:	Reduced average tumor volume relative to the control group at both 0.2 mg/kg and 0.4 mg/kg. Inhibited tumor growth to levels comparable to low-dose docetaxel groups.

Animal Model:	ICR (male, ~2 months old, 19−21 g)^[1]
Dosage:	2 mg/kg; 3 mg/kg; 5 mg/kg; 6 mg/kg; 7 mg/kg; 8 mg/kg; 9 mg/kg; 30 mg/kg; 45 mg/kg; 60 mg/kg
Administration:	i.v.; single dose
Result:	Resulted in a median lethal dose (LD₅₀) of 6.3 mg/kg. Produced a therapeutic index of 21, calculated as LD₅₀/ED₅₀.

Animal Model:	Wistar (male, ~2 months old, 190−210 g)^[1]
Dosage:	1 mg/kg; 2 mg/kg; 3 mg/kg; 4 mg/kg; 4.5 mg/kg; 5 mg/kg; 5.1 mg/kg; 5.4 mg/kg; 6 mg/kg; 8 mg/kg; 9 mg/kg; 15 mg/kg; 23 mg/kg; 30 mg/kg
Administration:	i.v.; single dose
Result:	Resulted in a median lethal dose (LD₅₀) of 4.9 mg/kg.

Animal Model:	Wistar (male, ~2 months old, 190−210 g)^[1]
Dosage:	150 μg/kg; 188 μg/kg; 225 μg/kg
Administration:	i.v.; once every three weeks; three months
Result:	Ensured all rats survived to the end of the experiment. Caused externally visible signs of intoxication (diarrhea resolving within seven days post-injection) only in the 225 μg/kg group. Induced dose-dependent hypo- and aplasia of spermatogenesis in the testes. Resulted in body weight changes significantly different from controls only at the highest dose, with changes not constant.

Animal Model:	Soviet Chinchilla (male, ~2 months old, 2.0−2.2 kg)^[1]
Dosage:	81 μg/kg; 102 μg/kg; 122 μg/kg
Administration:	i.v.; once every three weeks; three months
Result:	Caused one death in the 122 μg/kg group after the second injection; all other rabbits survived. Induced decreased blood lymphocyte counts and increased glucose levels. Caused hypo- and aplasia of spermatogenesis in some animals, with no clear dose-dependence. Resulted in body weight changes significantly different from controls only at the highest dose, with changes not constant.

Molecular Weight

2267.10

Formula

C₁₁₄H₁₆₅ClN₂₀O₂₆

CAS No.

2748039-79-2

Appearance

Solid

Color

White to off-white

SMILES

OC(CC[C@@H](C(O)=O)NC(N[C@@H](CCCCN(CC1=CC(Cl)=CC=C1)C(CCCCCNC(CCC(N[C@H](C(N[C@H](C(NCCCN2N=NC(CCCC(N[C@H](C(N[C@H](C(NC3=CC=C(C=C3)COC(N([C@H](C(N[C@@H](C(C)C)C(N([C@H]([C@@H](CC(N4CCC[C@]4([C@@H]([C@@H](C)C(N[C@@H]([C@H](C5=CC=CC=C5)O)C)=O)OC)[H])=O)OC)[C@@H](C)CC)C)=O)=O)C(C)C)C)=O)=O)CCCNC(N)=O)=O)C(C)C)=O)=C2)=O)CC6=CC=C(C=C6)O)=O)CC7=CC=CC=C7)=O)=O)=O)C(O)=O)=O)=O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

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

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (44.11 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	0.4411 mL	2.2055 mL	4.4109 mL
5 mM	0.0882 mL	0.4411 mL	0.8822 mL
10 mM	0.0441 mL	0.2205 mL	0.4411 mL

View the Complete Stock Solution Preparation Table

* 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, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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This equation is commonly abbreviated as: C₁V₁ = C₂V₂

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In Vivo Dissolution Calculator

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Working solution concentration: mg/mL

Purity & Documentation

Purity: 99.52%

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Data Sheet (293 KB) SDS (254 KB)

COA (263 KB) HNMR (477 KB) RP-HPLC (258 KB) LCMS (88 KB)

Handling Instructions (2659 KB)

References

[1]. Machulkin AE, et al. Synthesis, Characterization, and Preclinical Evaluation of a Small-Molecule Prostate-Specific Membrane Antigen-Targeted Monomethyl Auristatin E Conjugate. J Med Chem. 2021;64(23):17123-17145. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	0.4411 mL	2.2055 mL	4.4109 mL	11.0273 mL
	5 mM	0.0882 mL	0.4411 mL	0.8822 mL	2.2055 mL
	10 mM	0.0441 mL	0.2205 mL	0.4411 mL	1.1027 mL
	15 mM	0.0294 mL	0.1470 mL	0.2941 mL	0.7352 mL
	20 mM	0.0221 mL	0.1103 mL	0.2205 mL	0.5514 mL
	25 mM	0.0176 mL	0.0882 mL	0.1764 mL	0.4411 mL
	30 mM	0.0147 mL	0.0735 mL	0.1470 mL	0.3676 mL
	40 mM	0.0110 mL	0.0551 mL	0.1103 mL	0.2757 mL