BiochemProbe — Life Science Research Reagents

G-5555 free base · Synonyms: G 5555 · G5555

G-5555 is a potent p21-activated kinase 1 inhibitor.

For research use only. Not for human or veterinary use.

Target PAK
Research area Cancer
Purity >98% Stock Inquire
Data Sheet SDS COA

G-5555 structure

CAS No.: 1648863-90-4

Download structure (.mol)

Pack sizes & pricing

Size Price SKU Stock
100 mg USD 698.00 BP-02392-100mg In stock Get quote
250 mg USD 1,050.00 BP-02392-250mg In stock Get quote
500 mg USD 1,898.00 BP-02392-500mg In stock Get quote
1 g USD 2,798.00 BP-02392-1g In stock Get quote
2 g Inquire BP-02392-2g In stock Inquire

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Description

G-5555 is a potent p21-activated kinase 1 (PAK1) inhibitor with Kis of 3.7 nM and 11 nM for PAK1 and PAK2, respectively.

Biological activity

In Vitro G-5555 is a potent PAK1 inhibitor with a Ki of 3.7 nM. G-5555 shows excellent kinase selectivity and inhibits only eight out of the 235 kinases tested other than PAK1 with inhibition >70%: PAK2, PAK3, KHS1, Lck, MST3, MST4, SIK2, and YSK1. The IC50s of G-5555 against SIK2, PAK2, KHS1, MST4, YSK1, MST3 and Lck are 9, 11, 10, 20, 34, 43, 52 nM, respectively. In general, G-5555 demonstrates high selectivity for the group I PAKs. There is negligible activity for G-5555 against the hERG channel with IC50 more than 10 μM in a patch clamp assay[1]. G-5555 potently inhibits PAK2, with a Ki of 11 nM. In an array of 23 breast cancer cell lines, G-5555 has significantly greater growth inhibitory activity in cell lines that are PAK-amplified compared to non-amplified lines. In Vivo G-5555 exhibits low blood clearance and an acceptable half-life. Good oral exposure (AUC = 30 μM h) and high oral bioavailability (F = 80%) are achieved[1]. In an H292 non-small cell lunger cancer (NSCLC) xenograft study in mice, G-5555 inhibits phosphorylation of the PAK1/2 downstream substrate mitogen-activated protein kinase 1 (MEK1) S298 and, when administered at an oral dose of 25 mg/kg b.i.d., imparts 60% tumor growth inhibition in this model and a PAK1 amplified breast cancer xenograft model, MDAMB-175.

Identifiers

SMILES
ClC(C=C(C1=NC(C)=CC=C1)C=C2)=C2C3=CC4=CN=C(NC)N=C4N(C[C@@H]5OC[C@@H](N)CO5)C3=O
InChIKey
ZBCMHWUFWQFPLV-VVOJOOEHSA-N

Specifications

MW (average)
492.9570
Formula
C25H25ClN6O3
CAS No.
1648863-90-4
Physical state
Solid
Color
White to light yellow
Shipping
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage
Powder 4°C, sealed storage, away from moisture. In solvent -20°C, 1 month

Solubility

Soluble in DMSO

In vitro
DMSO : 25 mg/mL

Documents

References

[1]. Ndubaku CO, et al. Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pK a Polar Moiety. ACS Med Chem Lett. 2015 Oct 31;6(12):1241-6.
[2]. Rudolph J, et al. Chemically Diverse Group I p21-Activated Kinase (PAK) Inhibitors Impart Acute Cardiovascular Toxicity with a Narrow Therapeutic Window. J Med Chem. 2016 Jun 9;59(11):5520-41.

Same target

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Same research area

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