Nemorubicin - CAS 108852-90-0
Catalog number: 108852-90-0
Category: Inhibitor
Not Intended for Therapeutic Use. For research use only.
Molecular Formula:
C32H37NO13
Molecular Weight:
643.642
COA:
Inquire
Targets:
Microtubule/Tubulin
Description:
Nemorubicin, currently being developed by Nerviano, is a doxorubicin derivative that differs significantly from its parent drug in terms of spectrum of antitumor activity, metabolism and toxicity profile. The drug is active on tumors resistant to alkylating agents, topoisomerase II inhibitors and platinum derivatives. It works primarily through topoisomerase I inhibition. Of note, Nemorubicin is active in cells with upregulation of the nucleotide excision repair (NER) pathway, where current therapies fail. Nemorubicin is biotransformed in the liver into cytotoxic metabolites that may further contribute to render this drug highly active against primary liver tumors or liver metastases.
Purity:
>98%
Appearance:
white solid powder
Synonyms:
methoxymorpholinyldoxorubicin, PNU-152243A
MSDS:
Inquire
InChIKey:
CTMCWCONSULRHO-UHQPFXKFSA-N
InChI:
InChI=1S/C32H37NO13/c1-14-27(36)17(33-7-8-44-22(12-33)43-3)9-21(45-14)46-19-11-32(41,20(35)13-34)10-16-24(19)31(40)26-25(29(16)38)28(37)15-5-4-6-18(42-2)23(15)30(26)39/h4-6,14,17,19,21-22,27,34,36,38,40-41H,7-13H2,1-3H3/t14-,17-,19-,21-,22-,27+,32-/m0/s1
Canonical SMILES:
CC1C(C(CC(O1)OC2CC(CC3=C(C4=C(C(=C23)O)C(=O)C5=C(C4=O)C=CC=C5OC)O)(C(=O)CO)O)N6CCOC(C6)OC)O
Current Developer:
Nerviano Medical Sciences
1.Nemorubicin and doxorubicin bind the G-quadruplex sequences of the human telomeres and of the c-MYC promoter element Pu22.
Scaglioni L1, Mondelli R1, Artali R2, Sirtori FR3, Mazzini S4. Biochim Biophys Acta. 2016 Jun;1860(6):1129-38. doi: 10.1016/j.bbagen.2016.02.011. Epub 2016 Feb 23.
BACKGROUND: Intra-molecular G-quadruplex structures are present in the guanine rich regions of human telomeres and were found to be prevalent in gene promoters. More recently, the targeting of c-MYC transcriptional control has been suggested, because the over expression of the c-MYC oncogene is one of the most common aberration found in a wide range of human tumors.
2.LC-MS-MS determination of nemorubicin (methoxymorpholinyldoxorubicin, PNU-152243A) and its 13-OH metabolite (PNU-155051A) in human plasma.
Fraier D1, Frigerio E, Brianceschi G, James CA. J Pharm Biomed Anal. 2002 Oct 15;30(3):377-89.
A selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for quantitative determination of nemorubicin, (PNU-152243A, 3'-deamino-3'[2(S)-methoxy-4-morpholinyl]doxorubicin) hydrocloride and its reduced metabolite PNU-155051 in human plasma has been developed and validated. The method involved solid phase extraction (SPE) in 96-well plates. Plasma samples (0.5 ml plasma, spiked with doxorubicin as internal standard and diluted with 0.5 ml of 0.01 M borate buffer, pH 8.4) were extracted using Oasis HLB SPE material. The elution of PNU-152243, PNU-155051 and of IS was performed with 1 ml of methanol:0.1 M formic acid mixture (90:10, v/v). The organic phase was reduced to dryness under a stream of nitrogen at 20 degrees C and the residue was reconstituted with 0.25 ml of 10 mM ammonium formate buffer pH 4.15:acetonitrile mixture (90:10, v/v). Aliquots of 60 microl of the resulting solution were injected onto the LC-MS-MS system.
3.The interaction of nemorubicin metabolite PNU-159682 with DNA fragments d(CGTACG)(2), d(CGATCG)(2) and d(CGCGCG)(2) shows a strong but reversible binding to G:C base pairs.
Mazzini S1, Scaglioni L, Mondelli R, Caruso M, Sirtori FR. Bioorg Med Chem. 2012 Dec 15;20(24):6979-88. doi: 10.1016/j.bmc.2012.10.033. Epub 2012 Nov 3.
The antitumor anthracycline nemorubicin is converted by human liver microsomes to a major metabolite, PNU-159682 (PNU), which was found to be much more potent than its parent drug toward cultured tumor cells and in vivo tumor models. The mechanism of action of nemorubicin appears different from other anthracyclines and until now is the object of studies. In fact PNU is deemed to play a dominant, but still unclear, role in the in vivo antitumor activity of nemorubicin. The interaction of PNU with the oligonucleotides d(CGTACG)(2), d(CGATCG)(2) and d(CGCGCG)(2) was studied with a combined use of (1)H and (31)P NMR spectroscopy and by ESI-mass experiments. The NMR studies allowed to establish that the intercalation between the base pairs of the duplex leads to very stable complexes and at the same time to exclude the formation of covalent bonds. Melting experiments monitored by NMR, allowed to observe with high accuracy the behaviour of the imine protons with temperature, and the results showed that the re-annealing occurs after melting.
4.Formation and antitumor activity of PNU-159682, a major metabolite of nemorubicin in human liver microsomes.
Quintieri L1, Geroni C, Fantin M, Battaglia R, Rosato A, Speed W, Zanovello P, Floreani M. Clin Cancer Res. 2005 Feb 15;11(4):1608-17.
PURPOSE: Nemorubicin (3'-deamino-3'-[2''(S)-methoxy-4''-morpholinyl]doxorubicin; MMDX) is an investigational drug currently in phase II/III clinical testing in hepatocellular carcinoma. A bioactivation product of MMDX, 3'-deamino-3'',4'-anhydro-[2''(S)-methoxy-3''(R)-oxy-4''-morpholinyl]doxorubicin (PNU-159682), has been recently identified in an incubate of the drug with NADPH-supplemented rat liver microsomes. The aims of this study were to obtain information about MMDX biotransformation to PNU-159682 in humans, and to explore the antitumor activity of PNU-159682.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related Microtubule/Tubulin Products


CAS 474645-27-7 MMAE

MMAE
(CAS: 474645-27-7)

MMAE, whose full name is Monomethyl auristatin E, inhibits tubulin polymerization so that it inhibits cell division.

CAS 945771-74-4 BNC-105

BNC-105
(CAS: 945771-74-4)

BNC105 is a novel compound being developed by Bionomics as a Vascular Disrupting Agent (VDA) for treatment of cancer. VDAs are drugs that disrupt the blood vess...

CAS 74588-78-6 D-64131

D-64131
(CAS: 74588-78-6)

D-64131, under the IUPAC name (5-methoxy-1H-indol-2-yl)-phenylmethanone, is a 2-aroylindole derivatives that inhibits tubulin polymerization. In vitro: Inhibits...

CAS 204205-90-3 Indibulin

Indibulin
(CAS: 204205-90-3)

Indibulin, also called D 24851, estabilizes tubulin polymerization (IC50 = 0.3 μM) and induces tumor cell cycle arrest and apoptosis. In vitro: blocking cell cy...

CAS 441045-17-6 eribulinmesilate

eribulinmesilate
(CAS: 441045-17-6)

Eribulinmesilate can inhibit experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (EMT) to mesenchymal-e...

CAS 154554-41-3 CHM 1

CHM 1
(CAS: 154554-41-3)

CHM 1 is an apoptosis inducer with potent antitumor activity in human hepatocellular carcinoma. It inhibits tubulin polymerization in vitro and in vivo, and res...

CKD-516 HCl
(CAS: 1188371-47-2)

This active molecular is a tubulin polymerisation inhibitor which is applicated for solid cancer treatment. CKD-516 disruptes tubulin of the endothelial cytoske...

CAS 52205-73-9 Estramustine phosphate sodium

Estramustine phosphate sodium
(CAS: 52205-73-9)

Estramustine phosphate sodium is an antimicrotubule chemotherapy agent. It arrests prostate cancer cells in the G2/M phase of the cell cycle.

CAS 125317-39-7 Vinorelbine ditartrate

Vinorelbine ditartrate
(CAS: 125317-39-7)

Vinorelbine ditartrate, whose base is Vinorelbine, is a selective mitotic microtubule antagonist. It inhibits proliferation of Hela cells (IC50= 1.25 nM) and s...

CAS 917111-44-5 Lexibulin

Lexibulin
(CAS: 917111-44-5)

lexibulin, also known as CYT997,  is an orally bioavailable small-molecule with tubulin-inhibiting, vascular-disrupting, and potential antineoplastic activ...

EHT-6706 dihydrochloride
(CAS: 1351592-09-0)

EHT-6706 can target the colchicine-binding site to inhibit tubulin polymerization as a tubulin polymerisation inhibitor. It is under the development of Diaxonhi...

CAS 865-21-4 Vinblastine

Vinblastine
(CAS: 865-21-4)

Vinblastine is inhibitor of nAChR and can inhibit the formation of microtubule. It is a natural alkaloid isolated from the plant Vinca rosea Linn. It binds to t...

CAS 141430-65-1 ABT 751

ABT 751
(CAS: 141430-65-1)

ABT 751, also called E7010, is a a novel bioavailable tubulin-binding and antimitotic agent (in neuroblastoma: IC50= 0.6–2.6 μM; in non-neuroblastoma cell line...

CAS 729605-21-4 XRP44X

XRP44X
(CAS: 729605-21-4)

XRP44X, under the IUPAC name [4-(3-chlorophenyl)piperazin-1-yl]-(5-methyl-2-phenylpyrazol-3-yl)methanone, as an inhibitor of Tubulin it indirectly inhibits Net ...

CAS 6559-91-7 4'-Demethylepipodophyllotoxin

4'-Demethylepipodophyllotoxin
(CAS: 6559-91-7)

4'-Demethylepipodophyllotoxin is a key intermediate compound for the preparation of podophyllotoxin-type anti-cancer drugs. It is a potent inhibitor of microtub...

CAS 613-11-6 TRx 0237

TRx 0237
(CAS: 613-11-6)

TRx 0237, also called LMT-X or Methylene Blue, is a second-generation tau protein aggregation inhibitor currently in development for the treatment of Alzheimer'...

CAS 2068-78-2 Vincristine

Vincristine
(CAS: 2068-78-2)

Vincristine is an inhibitor of polymerization of microtubules by binding to tubulin with IC50 of 32 μM.

CAS 143-67-9 Vinblastine Sulfate

Vinblastine Sulfate
(CAS: 143-67-9)

Vinblastine sulfate, also called cellblastin, derived from C. roseus, as a microtubule disrupter and antineoplastic agent, it binds tubulin and disrupts microtu...

CAS 117048-59-6 Combretastatin A4

Combretastatin A4
(CAS: 117048-59-6)

Combretastatin A4, under the IUPAC name 2-methoxy-5-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenol, inhibits tubulin polymerization (IC50= 2.2 μM). It has demons...

ALB 109564(a) dihydrochloride
(CAS: 1300114-12-8)

ALB 109564(a) is a Tubulin inhibitor as a semi-synthetic derivative of the vinka alkaloid originated by AMRI. It can bind to tubulin monomers and inhibit microt...

Chemical Structure

CAS 108852-90-0 Nemorubicin

Quick Inquiry

Verification code

Featured Items