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Fig. 1 · Structure
Cat. No.
A10713
CAS No.
477575-56-7
Formula
C32H34Cl2N4O4S
Mol. Weight
641.6

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PHA-665752

Cat. No. A10713 CAS 477575-56-7

c-Met Inhibitor

PHA665752 is a small-molecule inhibitor of c-Met/HGF/SF signaling.

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Biological Activity

Target & Activity

Target Activity Value
c-Met IC50 9nM
RON IC50 68nM
Flk1 IC50 200nM
c-Abl IC50 1.4μM
FGFR1 IC50 3μM
EGFR IC50 3.8μM
c-Src IC50 6μM
IGF-1R IC50 >10μM
PDGFR IC50 >10μM
AuroraA2 IC50 >10μM
PKA IC50 >10μM
PKBα IC50 >10μM
CDK2 IC50 >10μM
p38α IC50 >10μM
MK2 IC50 >10μM
MK3 IC50 >10μM

16 targets · Scroll to view more

Cellular Effect

Cell Line Activity Value Description Reference
A549 IC50 9 nM Inhibition of human recombinant c-MET kinase expressed in A549 cells assessed as inhibition of HGF-induced autophosphorylation by ELISA method [PMID: 21812414]
HCC827 IC50 15.7 μM Cytotoxicity against erlotinib-sensitive human HCC827A cells assessed as reduction in cell viability after 72 hrs by MTT assay [PMID: 27563407]
HCC827 IC50 8.9 μM Cytotoxicity against erlotinib-resistant human HCC827B cells expressing MET assessed as reduction in cell viability after 72 hrs by MTT assay [PMID: 27563407]
TAMH IC50 8.9 μM Cytotoxicity against TAMH assessed as reduction in cell viability after 24 hrs by cell titer glo based luminescence assay [PMID: 27563407]

In Vitro Studies

PC-3 cells were treated with 2.5 μM added to each well. Treatment fully inhibited PC-3 cell growth, assessed by MTS assays. H69 cells grown in agar were treated with 0.5 μM. Colony formation was reduced under both non-stimulated and HGF-stimulated conditions (P<0.05). PC-3 cells were exposed to 0.5 μM for 3 hours and assessed by immunoblotting. Phosphorylated c-Met protein was not detected in inhibitor-treated samples. [1,2]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Growth inhibition in PC-3 cells

Cell-based study · PC-3 cells [1]

PC-3 cells were treated with 2.5 μM added to each well. Treatment fully inhibited PC-3 cell growth, assessed by MTS assays.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
growth of PC-3 and DU-145 cells by MTS assaysReported result fully inhibited the growth of PC-3 cells at 2.5 μM[1]

Literature-Reported Treatment Conditions

Treatment concentration
2.5 μM
Exposure duration
after 4 hours, and cells were then incubated for up to 8 days
Method
added to each well
Vehicle
DMSO
Methods and source locations

Compound reported in the paper: PHA-665752

Literature evidence for the named compound in the stated model; no Adooq product-use or lot-performance claim.

Methods > Cell proliferation and colony formation assays (S6, S7); Results > C-Met inhibitors decrease proliferation of AR negative prostate cancer cells (S40, S41)

growth of PC-3 and DU-145 cells by MTS assays: growth of PC-3 and DU-145 cells by MTS assays; comparator: Appropriate controls — Results > C-Met inhibitors decrease proliferation of AR negative prostate cancer cells (S40, S41)

Reduced colony formation in H69 cells

Cell-based study · H69 cells [2]

H69 cells grown in agar were treated with 0.5 μM. Colony formation was reduced under both non-stimulated and HGF-stimulated conditions (P<0.05).

Measured endpoints — not treatment concentrations
EndpointReported resultReference
The number and size of coloniesReported result reduced colony formation in H69 cells (Figure 2B), both in non-stimulated and HGF-stimulated conditions (P<0.05)[2]

Literature-Reported Treatment Conditions

Treatment concentration
0.5 μM
Exposure duration
cells were fed every 3 days
Method
grown in 0.3% agar
Vehicle
DMSO
Reported limits
Not stated in the sentences used: control.
Methods and source locations

Compound reported in the paper: PHA-665752

Literature evidence for the named compound in the stated model; no Adooq product-use or lot-performance claim.

Materials and methods > Cell lines and reagents (S6); Materials and methods > Soft-agar colony formation assay (S21, S22, S23); Results > PHA-665752 inhibits colony formation and invasiveness in MET mutant SCLC cells (S85)

The number and size of colonies: The number and size of colonies — Materials and methods > Soft-agar colony formation assay (S23); Results > PHA-665752 inhibits colony formation and invasiveness in MET mutant SCLC cells (S85)

Phosphorylated c-Met detection in PC-3 cells

Cell-based study · PC-3 [1]

PC-3 cells were exposed to 0.5 μM for 3 hours and assessed by immunoblotting. Phosphorylated c-Met protein was not detected in inhibitor-treated samples.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
immunoblotting with c-Met or phosphorylated c-Met antibodyReported result phosphorylated c-Met protein was not detected in the samples treated with the inhibitors[1]

Literature-Reported Treatment Conditions

Treatment concentration
0.5 μM
Exposure duration
3 hours
Method
exposed
Vehicle
DMSO
Methods and source locations

Compound reported in the paper: PHA-665752

Literature evidence for the named compound in the stated model; no Adooq product-use or lot-performance claim.

Results > C-Met inhibitors decrease proliferation of AR negative prostate cancer cells (S52); Figure 1 legend (S111, S112)

immunoblotting with c-Met or phosphorylated c-Met antibody: immunoblotting with c-Met or phosphorylated c-Met antibody; comparator: DMSO alone — Results > C-Met inhibitors decrease proliferation of AR negative prostate cancer cells (S52); Figure 1 legend (S112)

In Vivo Studies

Male C57BL/6 mice received PHA-665752 at 20 mg/kg i.p. daily following injury. Compared with the vehicle-treated group, PHA-665752-treated animals showed increased RNA levels of IL-1β, iNOS, and CCL2 and reduced levels of IL-10, TGF-β, arginase 1, CD163, and resistin-like alpha. [3]

Marker RNA changes in male mice

Animal study · ten-week-old male C57BL/6 mice [3]

Male C57BL/6 mice received 20 mg/kg i.p. daily following injury. Compared with the vehicle-treated group, treated animals showed increased RNA levels of IL-1β, iNOS, and CCL2 and reduced levels of IL-10, TGF-β, arginase 1, CD163, and resistin-like alpha.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
The RNA level of these genes isolated from TAs 3 days after injury was determined by RT-qPCRReported result In animals treated with PHA-665752, the level of IL-1β, iNOS, and CCL2 (M1 markers) further increased (Figure 3A), while that of IL-10, TGF-β, arginase 1 (Arg1), CD163, and resistin-like alpha (Retnla) (M2 markers) was reduced, in comparison to the vehicle-treated group (Figure 3B).[3]

Conditions shared by the study groups

Route
i.p.
Treatment course
on a daily basis until sacrificed
Vehicle
DMSO
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
PHA-665752 20 mg/kgvehicle-treated groupIn animals treated with PHA-665752, the level of IL-1β, iNOS, and CCL2 (M1 markers) further increased (Figure 3A), while that of IL-10, TGF-β, arginase 1 (Arg1), CD163, and resistin-like alpha (Retnla) (M2 markers) was reduced, in comparison to the vehicle-treated group (Figure 3B).[3]
PHA-665752 20 mg/kg
Model: ten-week-old male C57BL/6 mice
Methods and source locations

Compound reported in the paper: PHA-665752

Literature evidence for the named compound in the stated model; no Adooq product-use or lot-performance claim.

Materials and Methods > Surgical Procedures (S5, S7); Results > Inhibition of c-Met Signaling Delayed Muscle Regeneration (S72); Figure 3 legend (S158, S161)

The RNA level of these genes isolated from TAs 3 days after injury was determined by RT-qPCR: The RNA level of these genes isolated from TAs 3 days after injury was determined by RT-qPCR; comparator: vehicle-treated group — Results > Inhibition of c-Met Signaling Delayed Muscle Regeneration (S72); Figure 3 legend (S161)

PHA-665752 20 mg/kg · Results > Inhibition of c-Met Signaling Delayed Muscle Regeneration (S72); Figure 3 legend (S158)

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 477575-56-7
Applications c-Met Inhibitor
Formula C32H34Cl2N4O4S
Molecular Weight 641.6
SMILES
CC1=C(NC(=C1C(=O)N2CCC[C@@H]2CN3CCCC3)C)/C=C\4/C5=C(C=CC(=C5)S(=O)(=O)CC6=C(C=CC=C6Cl)Cl)NC4=O

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO 124 mg/mL (193.26 mM)
Water Insoluble
Ethanol Insoluble

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

In Vivo Preparation

Concentration
4 mg/mL
Vehicle
2% DMSO+castor oil

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Tu WH, Zhu C, Clark C, et al. Efficacy of c-Met inhibitor for advanced prostate cancer. BMC Cancer (2010). PMID: 20946682 DOI: 10.1186/1471-2407-10-556 Source material
  2. [2] Arriola E, Cañadas I, Arumí-Uría M, et al. MET phosphorylation predicts poor outcome in small cell lung carcinoma and its inhibition blocks HGF-induced effects in MET mutant cell lines. Br J Cancer (2011). PMID: 21847116 DOI: 10.1038/bjc.2011.298 Source material
  3. [3] Choi W, Lee J, Lee J, et al. Hepatocyte Growth Factor Regulates Macrophage Transition to the M2 Phenotype and Promotes Murine Skeletal Muscle Regeneration. Front Physiol (2019). PMID: 31404148 DOI: 10.3389/fphys.2019.00914 Source material

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