PD 151746 (PD-151746) is a novel, potent, selective, and cell-permeable calpain inhibitor with important biological activity. It has a selectivity for u-calpain (Ki = 0.26 ± 0.03 μM) that is roughly 20 times higher than that of m-calpain (Ki = 5.33 ± 0.77 μM), and it inhibits calpain with a Ki of 0.26 μM for μ-Calpain. PD151746 completely inhibited the fragmentation of calmodulin-dependent protein kinase II-α (CaMPK-IIα) and nitric oxide synthase (nNOS), which were cleaved by calpain, and significantly inhibited NMDA-induced α-spectrin breakdown product (SBDP) of 145 kDa. PD 151746, an μ-calpain inhibitor, reduces the cytotoxicity caused by oxLDL.

Physicochemical Properties

Molecular Formula	C11H8FNO2S
Molecular Weight	237.25
Exact Mass	237.026
Elemental Analysis	C, 55.69; H, 3.40; F, 8.01; N, 5.90; O, 13.49; S, 13.51
CAS #	179461-52-0
Related CAS #	179461-52-0
PubChem CID	5353866
Appearance	Light yellow to brown solid powder
Density	1.525±0.06 g/cm3
LogP	2.662
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	16
Complexity	321
Defined Atom Stereocenter Count	0
SMILES	O=C(O)/C(S)=C/C1=CNC2=C1C=C(F)C=C2
InChi Key	HWMQHECFXSVZGN-KMKOMSMNSA-N
InChi Code	InChI=1S/C11H8FNO2S/c12-7-1-2-9-8(4-7)6(5-13-9)3-10(16)11(14)15/h1-5,13,16H,(H,14,15)/b10-3-
Chemical Name	(Z)-3-(5-fluoro-1H-indol-3-yl)-2-sulfanylprop-2-enoic acid
Synonyms	PD 151746; PD151746; PD-151746
HS Tariff Code	2934.99.03.00
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	μ-Calpain (IC50 = 260 nM); m-calpain (IC50 = 5.33 μM)
ln Vitro	PD151746 efficiently reduces the SLLVY-AMC hydrolysis brought on by maitotoxin in SY5Y cells. (Source: ) PD 151746 reduces the cytotoxicity of oxidized low-density lipoprotein (oxLDL) in HMEC-1 cells.[2]
ln Vivo
Enzyme Assay	PD151746 is a calpain inhibitor that exhibits a 20-fold selectivity for u-calpain (Ki = 0.26 ± 0.03 μM) compared to m-calpain (Ki = 5.33 ± 0.77 μM).
Cell Assay	PD151746 prevented serum/potassium (S/K) withdrawal-induced apoptosis in cerebellar granule cells by 29% by blocking calpain. Moreover, PD151746 reduced caspase-3 activity, cdk5/p25 formation, and the rise in MEF2 phosphorylation. PD151746 dramatically decreased insulin-stimulated glycogen synthesis in human hepatoma G2 cells while increasing protein tyrosine phosphatase-ε (PTPε), suggesting that calpain was a key player in the regulation of insulin-stimulated glycogen synthesis. PD151746 elevated cytoplasmic free Ca2+ ([Ca2+]I) in HEK-293 cells expressing human formyl peptide receptor (hFPR) or hFPR-like 1 (hFPRL1).
Animal Protocol
References	[1]. Proc Natl Acad Sci U S A . 1996 Jun 25;93(13):6687-92. [2]. Biochem J . 2003 Sep 1;374(Pt 2):403-11.

Solubility Data

Solubility (In Vitro)

DMSO: ~47 mg/mL (~198.1 mM) Water: <1 mg/mL Ethanol: ~47 mg/mL (~198.1 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.2150 mL	21.0748 mL	42.1496 mL
	5 mM	0.8430 mL	4.2150 mL	8.4299 mL
	10 mM	0.4215 mL	2.1075 mL	4.2150 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.