Cellagen Technology LLC
 
작성일 : 16-10-12
[Cellagen Technology LLC] Disease Area, Oncology II
ABT-869 (Linifanib) l KDR, CSF-1R, FLT1/3, PDGFRb inhibitor / ABT-888 (veliparib) l PARP1/2 inhibitor / AC220 (Quizartinib) l FLT3 inhibitor / ACY-1215 (Rocilinostat) | HDAC6/8 inhibitor

 

Disease Area, Oncology II

 

 

Product Name: ABT-869 (Linifanib) l KDR, CSF-1R, FLT1/3, PDGFRb inhibitor (#C2869)

 

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ABT-869 (Linifanib) is an aminobenzopyrazole-based, orally available, ATP-competitive receptor tyrosine

kinase inhibitor with IC50 potency against KDR, FLT1, CSF-1R, FLT3, and PDGFRb of 4 nM, 3 nM, 3 nM,

4 nM, and 66 nM, respectively. It is highly selective (> 1uM) against unrelated tyrosine kinases and

serine/threonine kinases. [1] In cellular assays, ABT-689 exhibited potency against ligand-induced

PDGFRbeat, KIT, and CSF-1R phosphorylation, with IC50s of 2, 31, and 10 nM, respectively.

In vivo, ABT-869 is orally effective in a wide range of human xenograft models, including MV4-11, HT1080,

H526, DLD-1, A431, MX-1, MDA-231, MDA-435LM, and glioma 9L. [2] ABT-869 displays antiproliferative and

apoptotic effects on cancer cells dependent on mutant kinases, such as FLT3. Consequently, ABT-869 is in

clinical studies for the treatment of acute myeloid leukemia (AML). [3, 4] ABT-689 has been shown to induce

apoptosis through an AKT and GSK-3beta-dependent pathway, thus suggesting that combination therapies

with GSK-3beta inhibitors may be a promising approach to AML treatment. [3]

 

Details

Chemical Formula:

 

C21H18FN5O

CAS No.:

 

796967-16-3

Molecular weight:

 

375.41

Purity:

> 98%

Appearance:

 

White

Chemical name:

 

1-(4-(3-amino-1H-indazol-4-yl)phenyl)-3-(2-fluoro-5-methylphenyl)urea

Solubility:

 

Up to 100 mM in DMSO

Synonyms:

 

ABT-869, ABT 869, ABT869, AL-39324, AL39324, Linifanib

Storage:

   

For longer shelf life, store solid powder at 4oC desiccated, or DMSO solution

at -20oC

 

References

1. Albert et al., Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol. Cancer

   Ther. 2006, 5, 995-1006. Pubmed ID: 16648571

2. Zhou et al., ABT-869, a promising multi-targeted tyrosine kinase inhibitor: from bench to bedside. J.

   Hematol. Oncol. 2009, 2, 33-45. Pubmed ID: 19642998

3. Hernandez-Davies et al., The multitargeted receptor tyrosine kinase inhibitor linifanib (ABT-869) induces

   apoptosis through an Akt and glycogen synthase kinase 3?-dependent pathway. Mol. Cancer Ther.

   2011, 10, 949-959. Pubmed ID: 21471285   

4. Shankar et al., ABT-869, a multitargeted receptor tyrosine kinase inhibitor: inhibition of FLT3

   phosphorylation and signaling in acute myeloid leukemia. Blood, 2007, 109, 3400-3408.

   Pubmed ID: 19642998  

 

 

Product Name: ABT-888 (Veliparib) l PARP1/2 inhibitor (#C2888)

 

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ABT-888 (Veliparib) is an orally-available, benzimidazole-based inhibitor of poly(ADP-ribose) polymerase

with Ki values of 5.2 and 2.9 nM, for PARP1 and PARP2, respectively. [1] ABT-888 exhibits activity in C41

whole cells at an EC50 of 2 nM [2], and inhibits PAR formation in cells at an EC50 of 4.5 nM. [3]

ABT-888 efficiently crosses the blood-brain barrier and has been shown to potentiate DNA-damaging agents

such as temozolomide, cisplatin, carboplatin, cyclophosphamide, irinotecan, and radiation. [1, 4] Treatment

with temozolomide in the S phase generated higher levels of double-stranded DNA breaks and general

higher levels of cytoxicity.

 

Details

Chemical Formula:

 

C13H16N4O

CAS No.:

 

912444-00-9, 912445-05-7

Molecular weight:

 

244.29

Purity:

> 98%

Appearance:

 

White solid

Chemical name:

 

(R)-2-(2-methylpyrrolidin-2-yl)-1H-benzo[d]imidazole-4-carboxamide

Solubility:

 

Up to 75 mM in DMSO

Synonyms:

 

ABT-888, ABT 888, ABT888, Veliparib

Storage:

   

For longer shelf life, store solid powder at 4oC desiccated, or DMSO solution

at -20oC

 

References

1. Palma et al., The PARP inhibitor, ABT-888 potentiates temozolomide: correlation with drug levels and

   reduction in PARP activity in vivo. Anticancer Res. 2008, 28, 2625-2636. Pubmed ID: 19035287

2. Penning et al., Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-

   2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer. J. Med. Chem. 2009, 52,

   514-523. Pubmed ID: 19143569

3. Liu et al., Potentiation of temozolomide cytotoxicity by poly(ADP)ribose polymerase inhibitor ABT-888

   requires a conversion of single-stranded DNA damages to double-stranded DNA breaks. Mol. Cancer Res.

   2008, 6, 1621-1629. Pubmed ID: 18922977

4. Donawho et al., ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-

   damaging agents in preclinical tumor models. Clin. Cancer Res. 2007, 13(9), 2728-2737.

   Pubmed ID: 19143569

 

 

Product Name: AC220 (Quizartinib) | FLT3 inhibitor (#C2222)

 

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AC220 (Quizartinib) is an orally-available, imidazobenzothiazole-based inhibitor of Flt3, with an in vitro Kd of

2 nM. In vitro cell studies show that AC220 has a IC50 of 0.5 nM for MV-411 cells. [1] In a variety of leukemic

cell lines, AC220 inhibited Flt3 phosphorylation of MV4-11, MOLM-14, SEM-K2, and RS4-11 at IC50s of 1, 2, 4,

and 4 nM, respectively. Furthermore, inhibition of cell proliferation on these same lines were measured as

0.3, 0.1, 0.4, and >10000 nM, respectively. [2]

In a KinomeScan panel of 402 kinases, AC220 has a high degree of specificity toward Flt3 with only mild

inhibition of closely related RTKs such as KIT, PDGFR, RET, VEGFR2. [3]

Ina Flt3-ITD acute myeloid leukemia mouse model, AC220 was shown to extend significantly the survival at 1

mg/kg QD dosing, and eradicates tumors in a Flt3-dependent mouse xenograft model at 10 mg/kg. [3]

 

Details

Chemical Formula:

 

C29H32N6O4S

CAS No.:

 

950769-58-1

Molecular weight:

 

560.67

Purity:

> 98%

Appearance:

 

White solid

Chemical name:

  

 

Urea, N-[5-(1,1-dimethylethyl)-3-isoxazolyl]-N'-[4-[7-[2-(4-morpholinyl)ethoxy]

imidazo[2,1-b]benzothiazol-2-yl]phenyl]-

Solubility:

 

Up to 100 mM in DMSO

Synonyms:

 

AC-220, AC220, Quizartinib

Storage:

 

 

For longer shelf life, store solid powder at 4oC desiccated, or DMSO solution

at -20oC

 

References

1. Belli et al., AC220, a uniquely potent and selective FLT3 inhibitor, enhances the cytotoxiceffects of

   chemotherapeutic agents in cell culture and in mouse tumor xenografts. Ambit Biosciences ASH Poster,

   2009, Abstract 2052.

2. Gunawardane et al., INHIBITION OF FLT3 SIGNALING BOTH IN VITRO AND IN VIVO BY AC220, A SECOND

   GENERATION POTENT AND SELECTIVE FLT3 INHIBITOR. Ambit Biosciences AACR Poster, 2010,

   Abstract 3619.

3. Zarrinkar et al., AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute

   myeloid leukemia (AML). Blood 2009, 114(14), 2984-2992. Pubmed ID: 19654408

 

 

Product Name: ACY-1215 (Rocilinostat) | HDAC6/8 inhibitor (#C2121)

 

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ACY-1215 (Rocilinostat) is an orally-available, hydroxamic acid-based, selective inhibitor of HDAC6 and

HDAC8 with IC50 values of 5 nM and 100 nM, respectively. ACY-1215 is12-, 10-, and 11-fold less active

against HDAC1, HDAC2, and HDAC3, respecitvely, and has minimal activity (IC50 > 1 uM) against HDAC4,

HDAC5, HDAC7, HDAC9, HDAC11, Sirtuin1 and Sirtuin2. [1]

To demonstrate ACY-1215 selectivity for HDAC6, MM.1S cells were cultured with increasing doses of ACY-

1215 for 6 hours. Dose-dependent increased acetylated a-tubulin was observed at low doses (0.62 uM) with

no effect on histone acetylation.

ACY-1215 has been shown to work synergistically with bortezomib in multiple myeloma models.

 

Details

Chemical Formula:

 

C24H27N5O3

CAS No.:

 

1316214-52-4

Molecular weight:

 

433.5

Purity:

> 98%

Appearance:

 

White solid

Chemical name:

 

2-(diphenylamino)-N-(7-(hydroxyamino)-7-oxoheptyl)pyrimidine-5-carboxamide

Solubility:

 

Up to 100 mM in DMSO

Synonyms:

 

AC-1215, ACR1215, Rocilinostat

Storage:

   

For longer shelf life, store solid powder at 4oC desiccated, or DMSO solution

at -20oC

 

References

1. Santo et al., Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6

   inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood 2012, 119, 2579-2589.

   Pubmed ID: 22262760

 

 


Ordering informations

     

Catalog No.

Product Name

Size

C2869

ABT-869 (Linifanib) l KDR, CSF-1R, FLT1/3, PDGFRb inhibitor

5 mg, 25 mg & 100 mg

C2888

ABT-888 (veliparib) l PARP1/2 inhibitor

5 mg, 25 mg & 100 mg

C2222

AC220 (Quizartinib) l FLT3 inhibitor

2 mg, 10 mg & 50 mg

C2121

ACY-1215 (Rocilinostat) | HDAC6/8 inhibitor

2 mg, 10 mg & 50 mg

 

 

 

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