Cys-McMMAF (0.3 mg/kg, 3 mg/kg; intravenous injection; single dosage) shows moderate stability in cynomolgus monkeys with a short base time [1]. Pharmacokinetic study in nude mice (nu/nu) [1] Model/IV dose (mg/kg) Cmax (ng/mL) Tmax (hr) AUC0-336 (ng·h/mL) t1/2 (day) Non-tumor 1 0.192 8 14.6 2.1 Tumor 1 0.146 8 28.2 6.0 Non-tumor 10 0.951 8 58.5 3.0 Tumor 10 0.945 8 81.9/td> 2.9

[1]. Preclinical Development of an anti-5T4 Antibody-Drug Conjugate: Pharmacokinetics in Mice, Rats, and NHP and Tumor/Tissue Distribution in Mice. Bioconjug Chem. 2015 Nov 18;26(11):2223-32.

Depatuxizumab/Denintuzumab mafodotin has been investigated for the treatment of lymphoma, glioma, glioblastoma, malignant glioma, squamous cell carcinoma, and glioblastoma multiforme. Vorsetuzumab mafodotin is currently being investigated in the clinical trial NCT01677390 (SGN-75 Phase Ib study of SGN-75 in combination with everolimus for the treatment of patients with renal cell carcinoma). Denintuzumab mafodotin is an immunoconjugate composed of an anti-CD19 monoclonal antibody conjugated to the olretamine derivative monomethylolretamine F (MMAF), possessing potential antitumor activity. After administration of Denintuzumab mafodotin, the antibody partially targets the CD19 antigen on the surface of various B-cell-derived tumor cells. Following antibody/antigen binding and internalization, the immunoconjugate releases MMAF, which binds to microtubules and inhibits their polymerization. Inhibition of microtubule polymerization may lead to G2/M phase arrest and tumor cell apoptosis. This inhibits the growth of CD19-expressing tumor cells. CD19 is a B-cell antigen that is overexpressed in many different types of cancer cells. Depatuxizumab Mafodotin is an epidermal growth factor receptor (EGFR) inhibitor with potential antitumor activity. After intravenous infusion, depatuxizumab Mafodotin inhibits EGFR activity, thereby blocking EGFR-mediated signaling. This may inhibit the growth of EGFR-overexpressing tumor cells. EGFR is a receptor tyrosine kinase that is overexpressed in certain tumor cell types and plays a crucial role in tumor cell proliferation and tumor angiogenesis. Vorsetuzumab Mafodotin is an antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody targeting the extracellular domain of the human CD70 molecule conjugated to the olrestatin analogue monomethylolrestatin phenylalanine (MMAF), and has potential antitumor activity. Vorsetuzumab (mafodotin) selectively binds to the extracellular domain of CD70 on the surface of tumor cells. Upon internalization, the MMAF portion is released, binds to tubulin, and inhibits its polymerization, potentially leading to G2/M phase arrest, tumor cell apoptosis, and inhibition of the proliferation of CD70-overexpressing tumor cells. CD70 is a ligand for the co-stimulatory receptor CD27, belonging to the tumor necrosis factor (TNF) family, and is present on the surface of various cancer cells.

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Drug Indications
Currently, there are no approved indications.Mechanism of Action
Depatuxizumab is an EGFR chimeric monoclonal antibody linked to monomethylammonium sulfadiazine F (mMA) via a maleimide hexanoyl linker (mafodotin). Upon delivery to cancer cells, the mafodotin component binds to tubulin, inhibiting the exchange of GDP and GTP required for tubulin subunit polymerization to form microtubules. Inhibition of microtubule polymerization disrupts mitosis and interferes with vesicle transport in cancer cells.

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Pharmacodynamics
Selectively targets cancer cells expressing mutant epidermal growth factor receptor (EGFR) vIII or overexpressing wild-type EGFR. Depatuxizumab mafodotin acts on these cells by inhibiting microtubule aggregation, thereby disrupting mitosis and vesicle transport.

C52H83N7O13S

1046.3195335865

1045.576

1160590-05-5

1160590-05-5

86278355

White to off-white solid powder

1.4

5

15

31

73

1880

10

S(C[C@@H](C(=O)O)N)C1C(N(C(C1)=O)CCCCCC(N(C)[C@@H](C(C)C)C(N[C@@H](C(C)C)C(N(C)[C@@H]([C@@H](C)CC)[C@@H](CC(N1CCC[C@H]1[C@@H]([C@H](C(N[C@H](C(=O)O)CC1C=CC=CC=1)=O)C)OC)=O)OC)=O)=O)=O)=O

BXTJCSYMGFJEID-XMTADJHZSA-N

InChI=1S/C52H83N7O13S/c1-12-32(6)45(38(71-10)27-41(61)58-25-19-22-37(58)46(72-11)33(7)47(63)54-36(52(69)70)26-34-20-15-13-16-21-34)57(9)50(66)43(30(2)3)55-48(64)44(31(4)5)56(8)40(60)23-17-14-18-24-59-42(62)28-39(49(59)65)73-29-35(53)51(67)68/h13,15-16,20-21,30-33,35-39,43-46H,12,14,17-19,22-29,53H2,1-11H3,(H,54,63)(H,55,64)(H,67,68)(H,69,70)/t32-,33+,35-,36-,37-,38+,39?,43-,44-,45-,46+/m0/s1

(2S)-2-[[(2R,3R)-3-[(2S)-1-[(3R,4S,5S)-4-[[(2S)-2-[[(2S)-2-[6-[3-[(2R)-2-amino-2-carboxyethyl]sulfanyl-2,5-dioxopyrrolidin-1-yl]hexanoyl-methylamino]-3-methylbutanoyl]amino]-3-methylbutanoyl]-methylamino]-3-methoxy-5-methylheptanoyl]pyrrolidin-2-yl]-3-methoxy-2-methylpropanoyl]amino]-3-phenylpropanoic acid

Cys-McMMAF

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~200 mg/mL (~191.2 mM)

Solubility in Formulation 1: ≥ 5 mg/mL (4.78 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 5 mg/mL (4.78 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 5 mg/mL (4.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)