Name: Dolastatin 10
Brand: BOC Sciences
Price: 519 USD
Availability: MadeToOrder

Size

Price

Stock

Quantity

5 mg

$519

In stock

25 mg

$999

In stock

Synonyms

DLS 10; NSC 376128; Dolastatin-10; DLS-10; DLS10; NSC376128; 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-,[2S-[1[1R*(R*),2S*],2R*[1S*,2S*,3(R*)]]]-

IUPAC Name

(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

Canonical SMILES

CCC(C)C(C(CC(=O)N1CCCC1C(C(C)C(=O)NC(CC2=CC=CC=C2)C3=NC=CS3)OC)OC)N(C)C(=O)C(C(C)C)NC(=O)C(C(C)C)N(C)C

InChI

1S/C42H68N6O6S/c1-13-28(6)37(47(10)42(52)35(26(2)3)45-40(51)36(27(4)5)46(8)9)33(53-11)25-34(49)48-22-17-20-32(48)38(54-12)29(7)39(50)44-31(41-43-21-23-55-41)24-30-18-15-14-16-19-30/h14-16,18-19,21,23,26-29,31-33,35-38H,13,17,20,22,24-25H2,1-12H3,(H,44,50)(H,45,51)/t28-,29+,31-,32-,33+,35-,36-,37-,38+/m0/s1

InChIKey

OFDNQWIFNXBECV-VFSYNPLYSA-N

Density

1.116±0.06 g/cm3 (Predicted)

Solubility

Soluble in DMSO (10 mm), water

Flash Point

500.3±34.3 °C

Index Of Refraction

1.537

PSA

161.65000

Vapor Pressure

0.0±0.3 mmHg at 25°C

Appearance

White to off-white solid

Shelf Life

≥360 days if stored properly

Shipping

Room temperature, or blue ice upon request.

Storage

Store at -20°C

Boiling Point

903.6±65.0°C (Predicted)

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 GI50 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.

NCT Number	Condition Or Disease	Phase	Start Date	Sponsor	Status
NCT00003778	Ovarian Cancer	Phase 2	2013-02-08	National Cancer Institute (NCI)	Completed
NCT00003693	Leukemia	Phase 1	2018-10-25	M.D. Anderson Cancer Center	Completed
NCT00003914	Kidney Cancer	Phase 2	2011-05-11	Mayo Clinic	Completed
NCT00003677	Pancreatic Cancer	Phase 2	2018-10-25	M.D. Anderson Cancer Center	Completed
NCT00005579	Leukemia	Phase 2	2013-06-26	University of Vermont	Completed

1.A synthetic dolastatin 10 analogue suppresses microtubule dynamics, inhibits cell proliferation, and induces apoptotic cell death.

Gajula PK1, Asthana J, Panda D, Chakraborty TK. J Med Chem. 2013 Mar 28;56(6):2235-45. doi: 10.1021/jm3009629. Epub 2013 Mar 19.

We have synthesized eight analogues (D1-D8) of dolastatin 10 containing several unique amino acid subunits. Of these agents, D5 was found to be most effective in inhibiting both HeLa cell proliferation and microtubule assembly in vitro. At low nanomolar concentrations, D5 inhibited the proliferation of several types of cancer cells in culture. D5 bound to tubulin with a dissociation constant of 29.4 ± 6 μM. D5 depolymerized microtubules in cultured cells and produced mulitpolar spindles. At its half-maximal inhibitory concentration (15 nM), D5 strongly suppressed the dynamics of individual microtubules in live MCF-7 cells. D5 increased the accumulation of checkpoint proteins BubR1 and Mad2 at the kinetochoric region and caused G2/M block in these cells. The blocked cells underwent apoptosis with the activation of Jun N-terminal kinase. The results suggested that D5 exerts its antiproliferative action by dampening microtubule dynamics.

2.Discovery of cytotoxic dolastatin 10 analogues with N-terminal modifications.

Maderna A1, Doroski M, Subramanyam C, Porte A, Leverett CA, Vetelino BC, Chen Z, Risley H, Parris K, Pandit J, Varghese AH, Shanker S, Song C, Sukuru SC, Farley KA, Wagenaar MM, Shapiro MJ, Musto S, Lam MH, Loganzo F, O'Donnell CJ. J Med Chem. 2014 Dec 26;57(24):10527-43. doi: 10.1021/jm501649k. Epub 2014 Dec 9.

Auristatins, synthetic analogues of the antineoplastic natural product Dolastatin 10, are ultrapotent cytotoxic microtubule inhibitors that are clinically used as payloads in antibody-drug conjugates (ADCs). The design and synthesis of several new auristatin analogues with N-terminal modifications that include amino acids with α,α-disubstituted carbon atoms are described, including the discovery of our lead auristatin, PF-06380101. This modification of the peptide structure is unprecedented and led to analogues with excellent potencies in tumor cell proliferation assays and differential ADME properties when compared to other synthetic auristatin analogues that are used in the preparation of ADCs. In addition, auristatin cocrystal structures with tubulin are being presented that allow for the detailed examination of their binding modes. A surprising finding is that all analyzed analogues have a cis-configuration at the Val-Dil amide bond in their functionally relevant tubulin bound state, whereas in solution this bond is exclusively in the trans-configuration.