|
|
| | dolastatin 10 Basic information |
| Product Name: | dolastatin 10 | | Synonyms: | (2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-N-[(3R,4S,5S)-3-methoxy-1-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide;Dolastain10;Dolastatin 10 (NSC-376128);L-Valinamide, N,N-dimethyl-L-valyl-N-[2-methoxy-4-[2-[1- methoxy-2-methyl-3-oxo-3-[[2-phenyl-1-(2-thiazolyl)ethyl] amino]propyl]-1-pyrrolidinyl]-1-(1-methylpropyl)-4-oxobutyl]-N-methyl-;dolastatin 10;B720389K560;From dolabella auricularia (sea hare);L-Valinamide, N,N-dimethyl-L-valyl-N-[2-methoxy-4-[2-[1- methoxy-2-methyl-3-oxo-3-[[2-phenyl-1-(2-thiazolyl)ethyl] amino]propyl]-1-pyrrolidinyl]-1-(1-methylpropyl)-4-oxobutyl]-N-methyl-, [2S-[1[1R*(R*),2S*],2R*[1S*,2S*,3(R*)]]]- | | CAS: | 110417-88-4 | | MF: | C42H68N6O6S | | MW: | 785.09 | | EINECS: | | | Product Categories: | ADCs | | Mol File: | 110417-88-4.mol |  |
| | dolastatin 10 Chemical Properties |
| Melting point | 107～112 | | Boiling point | 903.6±65.0 °C(Predicted) | | density | 1.116±0.06 g/cm3(Predicted) | | storage temp. | Store at -20°C,unstable in solution, ready to use. | | solubility | ≥78.5 mg/mL in EtOH; insoluble in H2O; ≥67.2 mg/mL in DMSO | | pka | 13.81±0.46(Predicted) | | form | Powder | | color | White to off-white | | optical activity | -6829 (methanol) |
| RIDADR | 3172 | | HazardClass | 6.1(b) | | PackingGroup | III |
| | dolastatin 10 Usage And Synthesis |
| Definition | ChEBI: Dolastatin 10 is a tetrapeptide that is isolated from the sea hare Dolabella auricularia. It is a potent anticancer agent which inhibits tubulin polymerization. It has a role as an animal metabolite, a marine metabolite, an antineoplastic agent, an apoptosis inducer and a microtubule-destabilising agent. It is a member of 1,3-thiazoles and a tetrapeptide. It is functionally related to a L-valine. | | Biological Activity | dolastatin 10 is an antitumor agent [1].dolastatin 10 is a potent antimitotic polypeptide isolated from a marine animal and is developed as a potential antitumor agent. dolastatin 10 is found to have activity to inhibit tubulin polymerization with ic50 value of 1.2μm. besides that, it potently inhibits vincristine binding to tubulin with a ki value of 1.4μm in a noncompetitive manner. dolastatin 10 also shows moderate effect on enhancing the binding of colchicines to tubulin. in addition, dolastatin 10 has the inhibitory activity in tubulin-dependent gtp binding [1].in the cellular assay, dolastatin 10 shows activity against some human leukaemia, lymphoma and solid tumour cell lines (such as ovcar-3 and nsclc) with ic50 values ranging from 0.1nm to 10nm. it is currently tested in the | | in vitro | Dolastatin 10 is a unique pentapeptide that isolated from the sea hare Dolabella auricularia . These in vitro data are quite comparable to those of Dolastatin 10 and Auristatin PE, each of which has GI < sub> 50 values of 10 ?5 -10 ?6 μg/mL (10 ?2 -10 ? 3 nM) against a similar minipanel of human cell lines. The antibody-drug conjugate (ADC) comprises the anti-CD30 monoclonal antibody cAC10 conjugated to the cytotoxic agent monomethyl auristatin E (MMAE), a synthetic analog of the tubulin polymerization inhibitor Dolastatin 10. | | target | | | references | [1] bai r l, pettit g r, hamel e. binding of dolastatin 10 to tubulin at a distinct site for peptide antimitotic agents near the exchangeable nucleotide and vinca alkaloid sites. journal of biological chemistry, 1990, 265(28): 17141-17149.
[2] schwartsmann g. marine organisms and other novel natural sources of new cancer drugs. annals of oncology, 2000, 11(suppl 3): 235-243. |
| | dolastatin 10 Preparation Products And Raw materials |
| Raw materials | 2-PyrrolidinepropanaMide, β-Methoxy-α-Methyl-N-[(1S)-2-phenyl-1-(2-thiazolyl)ethyl]-, (αR,βR,2S)--->Carbamic acid, [(1S,2S)-1-formyl-2-methylbutyl]methyl-, phenylmethyl ester (9CI)-->Heptanoic acid, 3-hydroxy-5-methyl-4-[methyl[(phenylmethoxy)carbonyl]amino]-, 1,1-dimethylethyl ester, [3S-(3R*,4R*,5R*)]- (9CI)-->benzyl ((2S,3S)-1-hydroxy-3-methylpentan-2-yl)(methyl)carbamate-->Heptanoic acid, 3-methoxy-5-methyl-4-[methyl[(phenylmethoxy)carbonyl]amino]-, 1,1-dimethylethyl ester, [3S-(3R*,4R*,5R*)]- (9CI)-->N-Cbz-L-Isoleucine-->N-BOC-L-Prolinal-->1-Pyrrolidinecarboxylic acid, 2-[(1R,2R)-1-Methoxy-2-Methyl-3-oxo-3-[[(1S)-2-phenyl-1-(2-thiazolyl)ethyl]aMino]propyl]-, 1,1-diMethylethyl ester, (2S)--->SXCDYMWHVBJDJZ-ZXHYAQOVSA-N-->N,N-DIMETHYL-L-VALINE-->(3R,4S,5S)-tert-butyl 3-Methoxy-5-Methyl-4-(MethylaMino)heptanoate hydroc hloride-->N-Boc-(2R,3R,4S)-dolaproine-->BOC-L-Isoleucine |
|