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Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic
USD 100+
Accessible (Haz class 3, 4, 5 or 8), International
Tubulin normally undergoes a cycle of detyrosination/tyrosination on the carboxy terminus of its alpha-subunit and this results in subpopulations of tyrosinated tubulin and detyrosinated tubulin[1]. Maytansinoid DM4 is a thiol-containing maytansine derivative with highly potent cytotoxicity. Maytansinoid DM4 is a tubulin inhibitor, inhibits the assembly of microtubules by binding to tubulin, with a linker structure can create an antibody-drug conjugate (ADC). Maytansine is a natural benzoansamacrolide product isolated from the bark of the African shrub Maytenus ovatus. Maytansine binds to the same site on tubulin as the vinca alkaloids, with similar in vitro inhibition constants, but is a more-potent cytotoxin[2]. Maytansinoid DM1 and DM4 inactivated CYP3A from human liver microsomes with K(i)/k(inact) values of 4. 8 ± 0. 9 μM/0. 035 ± 0. 002 min(-1) and 3. 3 ± 0. 2 μM/0. 114 ± 0. 002 min(-1), respectively. DM1 and DM4 inactivated recombinant CYP3A4 with K(i)/k(inact) values of 3. 4 ± 1. 0 μM/0. 058 ± 0. 005 min(-1) and 1. 4 ± 0. 3 μM/0. 117 ± 0. 006 min(-1), respectively[3]. Although S-methyl-DM1 and S-methyl-DM4 inhibited polymerization more weakly than maytansine, at 100 nmol/L they suppressed dynamic instability more strongly than maytansine (by 84% and 73%, respectively, compared with 45% for maytansine). Both maytansine and S-methyl-DM1 bound to tubulin with similar K(D) values (0. 86 ± 0. 2 and 0. 93 ± 0. 2 μmol/L, respectively)[4].
DM4 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Microtubule protein
100 nmol/L
40 minutes
To evaluate the effect of DM4 on microtubule dynamic instability, results showed that DM4 significantly suppressed microtubule dynamic instability, reducing the shortening rate by 56% and dynamicity by 73%.
Mol Cancer Ther. 2010 Oct;9(10):2689-99
Microtubule protein
0 – 20 μmol/L
45 minutes
To evaluate the inhibitory effect of DM4 on microtubule polymerization, results showed that DM4 inhibited microtubule polymerization at 1.7 ± 0.4 μmol/L.
Mol Cancer Ther. 2010 Oct;9(10):2689-99
NXS2 cells
3nM
72 hours
To evaluate the effect of DM4 on PD-L1 expression, results showed that DM4 significantly upregulated the surface expression of PD-L1.
J Transl Med. 2025 Apr 11;23(1):431
NXS2 cells
5nM
72 hours
To assess the ability of DM4 to induce immunogenic cell death (ICD), results showed that DM4 significantly upregulated the expression of calreticulin, HSP70, and HSP90.
J Transl Med. 2025 Apr 11;23(1):431
NXS2 CTRL and NXS2 hLGALS3BP cells
0.00064nM to 250nM
72 hours
To evaluate the cytotoxic effect of DM4 on neuroblastoma cells, results showed that DM4 exhibited potent cytotoxic activity with an IC50 in the nanomolar range (0.32 nM).
Evaluate the antitumor efficacy of T4H11-DM4 in xenograft models, complete tumor regression was achieved at doses of 5 and 10 mg/kg in HT-29 and HCT116 tumor models
Mol Oncol. 2019 Sep;13(9):1855-1873
Mice
A375-MA1 xenograft model
Intravenous injection
6.0-6.7 μg
Single dose, observed for 120 hours
To evaluate the pharmacokinetics and tumor uptake of [89Zr]Zr-DFO-1959-sss/DM4 in the A375-MA1 xenograft model
Mol Pharm. 2023 Jun 5;20(6):3241-3248
Nude mice
GBM patient-derived xenograft model
Intravenous injection
10 mg/kg
Twice weekly for a total of three injections
Evaluate the antitumor activity of 1959-sss/DM4 in GBM xenograft model
To evaluate the antitumor activity of anti-LGALS3BP ADC in a neuroblastoma model, results showed that ADC significantly shrank hLGALS3BP-expressing tumors and improved survival.
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