GY1-22 is an inhibitor (blocker/antagonist) of DNAJA1-mutP53R175H interaction. GY1-22 may be utilized in cancer-related research.

Physicochemical Properties

Molecular Formula	C23H20N4OS
Molecular Weight	400.496103286743
Exact Mass	400.135
CAS #	326903-84-8
PubChem CID	1357408
Appearance	Typically exists as solid at room temperature
LogP	5
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	7
Heavy Atom Count	29
Complexity	517
Defined Atom Stereocenter Count	0
InChi Key	SAJTUGXPTDYULN-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H20N4OS/c1-2-8-17(9-3-1)28-15-14-27-21-13-7-6-12-20(21)26-23(27)29-16-22-24-18-10-4-5-11-19(18)25-22/h1-13H,14-16H2,(H,24,25)
Chemical Name	2-(1H-benzimidazol-2-ylmethylsulfanyl)-1-(2-phenoxyethyl)benzimidazole
HS Tariff Code	2934.99.9001
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	DNAJA1-mutP53R175H interacting pocket[1]
ln Vitro	GY1-22 (0-50 μM; 24 h) decreases the production of mutant p53 protein in human colon cancer LS123 cells and mice pancreatic cancer P03. In mutp53-driven P03 cells, GY1-22 increases wtp53-activated Waf1p21 expression and inhibits cyclin D1 expression [1]. Following critical changes at the DNAJA1-mutp53 R175H complex interface, GY1-22 is unable to degrade mutp53R175H [1]. In mutp53-driven P03 pancreatic cancer cells, GY1-22 (0-100 μM; 24 h) exhibits modest cytotoxicity and dose-dependently suppresses cell proliferation [1].
ln Vivo	In rats, GY1-22 has an LD50 of 1240 mg/kg. After giving mice a dosage of 10 mg/kg (i.p.; daily for two weeks), there was no evidence of gross or histological harm [1]. For two weeks, GY1-22 (1 mg/kg; intraperitoneal; daily) suppresses the growth of P03 pancreatic cancer cells in mice driven by mutp53 [1].
Cell Assay	Western Blot Analysis[1] Cell Types: Mouse mutp53-driven P03 pancreatic cancer cells and human colon cancer LS123 cells Tested Concentrations: 0, 1, 10, 25 and 50 μM Incubation Duration: 24 h Experimental Results: decreased mutp53 protein expression in both cells. demonstrated a dose-dependent effect on inhibition of mutp53 and cyclin D1 expression but induction of wtp53-activated Waf1p21 expression tested in P03 cells. Cell Viability Assay[1] Cell Types: Mouse mutp53-driven P03 pancreatic cancer cells Tested Concentrations: 0, 25, 50, 75 and 100 μM Incubation Duration: 24 h Experimental Results: demonstrated a dose-dependent effect on inhibiting cell growth with IC50 of 28 μM and low cytotoxicity (cell viability).
Animal Protocol	Animal/Disease Models: C57BL/6J mice implanted with P03 cells[1] Doses: 1 mg/kg Route of Administration: IP, daily for 2 weeks Experimental Results: demonstrated a significant inhibition of in vivo tumor growth, which was comparable with P03 DNAJA1 knockout line.
References	[1]. Identification of a druggable protein-protein interaction site between mutant p53 and its stabilizing chaperone DNAJA1. J Biol Chem. 2021 Jan-Jun;296:100098.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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	2.4969 mL	12.4844 mL	24.9688 mL
	5 mM	0.4994 mL	2.4969 mL	4.9938 mL
	10 mM	0.2497 mL	1.2484 mL	2.4969 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.