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작성일 : 14-02-25
[Chemdea] PI3K/mTOR Inhibitors (4)


PI3K/mTOR Inhibitors (4)

 

Product Name: PKI-179 – PI3Ka/mTOR Inhibitor

 

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PKI-179 is an orally efficacious dual PI3K/mTOR inhibitor.  PKI-197 potently inhibited in in vitro enzymatic assay PI3Ka,

PI3Kg and mTORC1/mTORC2 (IC50 = 8 mM, 74 nM and 0.42 nM respectively) and it showed significant activity against

MDA-361 and PC3mm2 cell lines (IC50 = 22 mM, 29 nM respectively). PKI-179 showed excellent selectivity against 361-

membered kinase panel (IC50 > 50 mM). Pharmacokinetic studies of PKI-197 showed good oral bioavailability (98% in 

nude mouse, 46% in rat, 38% in monkey and 61% in dog) and high half-life (>60 min).  Evaluation of in vivo efficacy in

nude mouse model bearing MDA-361 human breast cancer tumors showed pronounced tumor growth arrest when dosed

above 10 mg/Kg.

 

Details

Chemical Formula:

 

C25H28N8O3*HCl.

CAS No.:

 

1197160-28-3

Molecular weight:

 

525.00

Purity:

97% by HPLC

Appearance:

 

White solid

Chemical name:

 

3-(4-Morpholinothieno[3,2-d]pyrimidin-2-yl)phenol dihydrochloride

Solubility:

 

DMSO (35 mg/mL). The hydrochloride form shows improved solubility as compared to the free base form.

Storage:

Protect from light. Packaged under inert gas

 

Reference

 

Product Name: pp121 – Tyrosin Kinase and PI3K Pathway Inhibitor

 

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A cell-permeable pyrazolopyrimidine compound that effectively targets the ATP pocket of both protein tyrosine kinases

(IC50 <0.26 μM against Abl, EGFR, EphB4, Hck, PDGFR, RET, Src, Src, and VEGFR2) and PI3-K T338I family kinases (IC50 

<1.4 μM against p110α/β/δ/γ, mTOR, and DNA-PK). PP121 is less effective against ser/thr kinases and exhibits

significant inhibition of only 14 ser/thr kinases (70% inhibition with 1 μM inhibitor and 10 mM ATP) in a 219 kinase panel

screening. Individually targeting Ret by sorafenib (IC50 = 780 nM) or PI3-K/mTOR pathway by PI-103 (IC50 = 800 nM) is

shown to be less effective than PP121 treatment (IC50 = 50 nM) in inhibiting the proliferation of Ret C634W-expressing TT

thyroid carcinoma cultures. 

 

Details

Chemical Formula:

 

C23H27N7O3S2

CAS No.:

 

C17H17N7

Molecular weight:

 

319.4

Purity:

99% by HPLC

Appearance:

 

White solid

Chemical name:

 

1-Cyclopentyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1Hpyrazolo[3,4-d]pyrimidin-4-amine

Solubility:

 

DMSO (100 mg/mL), ethanol (50 mg/mL)

Storage:

Protect from light. Packaged under inert gas

 

Reference

 

 

Product Name: PX-13-17OH – PI3K Inhibitor

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PX-13-17OH is an irreversible, isoform non-specific Wortmannin analog which potently inhibits PI3Ka/b/g/d (IC50 = 6.4

nM, 13 nM, 8 nM and 11 nM respectively). PX-13-17OH does not appreciably inhibit mTOR (IC50 = 2.92 mM). In a kinase 

panel PX-13-17OH did not show significan inhibition of other kinases (IC50 > 10 mM). In a cellular assay PX-13-17OH 

inhibited the LNCap cell line (IC50 = 0.39 mM). In a nude mouse xenograft model (U87MG glioma) PX-13-17OH showed

potent inhibition of tumor growth aldeardy at 1.25 mg/Kg in iv dosing. See also our product PX-866-17OH (Cat# CD0323)

and 17-b-Hydroxywortmannin (Cat# CD0278) with similar activity.

 

Details

Chemical Formula:

 

C29H42N2O8

CAS No.:

 

884539-95-1

Molecular weight:

 

546.65

Purity:

98% by HPLC

Appearance:

 

Yellow solid

Chemical name:

 

(1E,4S,4aR,5R,6aS,7S,9aR)-5-(Acetyloxy)-1-[[[3-(dimethylamino)propyl]methylamino]methylene]-4a,5,6,6a,7,8,9,9a-octahydro-7,11-dihydroxy-4-(methoxymethyl)-4a,6a-dimethylcyclopenta[5,6]na-phtho[1,2-c]pyran-2,10(1H,4H)-dione

Solubility:

 

DMSO (80 mg/mL), water (10 mg/mL).

Storage:

Protect from light. Packaged under inert gas

 

Reference

 

 

Product Name: PX-866

 

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Biologically stable, semisynthetic derivative of wortmannin. PX-866 is more potent that its parent compound,

wortmannin. PX-866 is a PI3-K inhibitor with selectivity for p110α.

 

Administered to mice at 10 mg/kg inhibited phospho-Ser473-Akt in HT-29 colon tumor xenografts up to 80% with

recovery taking >48 hours after p.o. administration but more rapidly after i.v. or i.p. administration. PX-866 exhibited in

vivo antitumor activity against s.c. OvCar-3 human ovarian cancer and A-549 human lung cancer xenografts in

immunodefficient mice with log cell kills up to 1.2.

 

 A major toxicity of PX-866 administration was hyperglycemia with decreased glucose tolerance, which was reversed upon

cessation of treatment. The decreased glucose tolerance caused by PX-866 was insensitive to the AMP-activated protein

kinase inhibitor metformin but reversed by insulin and by the peroxisome proliferator-activated receptor-γ activator

pioglitazone.

 

PX-866 increases the antitumor effects of cisplatin and radiation treatment.

 

Details

Chemical Formula:

 

C29H35NO8

CAS No.:

 

502632-66-8

Molecular weight:

 

525.6

Purity:

98% by HPLC

Appearance:

 

Yellow solid

Chemical name:

 

 (1E,4S,4aR,5R,6aS,9aR)- 5-(Acetyloxy)-1-[(di-2-propen-1-ylamino)methylene]-4,4a,5,6,6a,8,9,9a-octahydro-11-hydroxy-4-(methoxymethyl)-4a,6a-dimethylcyclopenta[5,6]naphtho[1,2-c]pyran-2,7,10(1H)-trione

Solubility:

 

DMSO, MeOH

Storage:

Protect from light. Packaged under inert gas

 

References

 

Product Name: PX-866-17OH – PI3K Inhibitor

 

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A cell-permeable, potent, reversible and specific phosphatidylinositol 3-kinase inhibitor (IC50 = 1.4 µM) that acts on the

ATP-binding site of the enzyme. Also inhibits nonhomologous DNA end-joining (NHEJ) activity of the 460 kDa

phosphatidylinositol 3-like kinase DNA-PKcs, which is the catalytic subunit of DNA-activated protein kinase. Does not affect

the activities of EGF receptor kinase, MAP kinase, PKC, Pl 4-kinase, S6 kinase, and c-Src even at 50 µM. Blocks the 

proliferation of cultured rabbit aortic smooth muscle cells without inducing apoptosis.

 

Details

Chemical Formula:

 

C29H37NO8

CAS No.:

 

1012327-63-7

Molecular weight:

 

527.61.

Purity:

> 99% by HPLC.

Appearance:

 

Yellow solid

Chemical name:

 

 (1E,4S,4aR,5R,6aS,7S,9aR)- 5-(Acetyloxy)-1-[(di-2-propen-1-ylamino)methylene]-4a,5,6,6a,7,8,9,9a-octahydro-7,11-dihydroxy-4-(methoxymethyl)-4a,6a-dimethylcyclopenta[5,6]naphtho[1,2-c]pyran-2,10(1H,4H)-dione

Solubility:

 

DMSO (50 mg/mL)

Storage:

Protect from light. Packaged under inert gas

 

References

 

 

Ordering informations

 

Catalog No.

Product Name

Size

CD0296

PKI-179 – PI3Ka/mTOR Inhibitor

1mg, 5mg, 10mg, 25mg,

50mg & 100mg

CD0257

pp121 – Tyrosin Kinase and PI3K Pathway Inhibitor

1mg, 5mg, 10mg, 25mg,

50mg, 100mg & 200mg

CD0305

PX-13-17OH – PI3K Inhibitor

1mg, 5mg, 10mg, 25mg,

50mg & 100mg

CD0279

PX-866

Inquire

CD0323

PX-866-17OH – PI3K Inhibitor

1mg, 5mg, 10mg,

25mg & 50mg

 

 

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