PROTAC BRAF-V600E degrader-1 is a potent degrader of PROTAC BRAF-V600E with Kd of 2.4 nM and 2 nM for BRAF and BRAF-V600E respectively. PROTAC BRAF-V600E degrader-1 degrades BRAF-V600E through the ubiquitin-proteasome system (UPS). PROTAC BRAF-V600E degrader-1 suppresses the growth of melanoma cells.

Physicochemical Properties

Molecular Formula	C48H54F2N10O10S
Molecular Weight	1001.0652
Exact Mass	1000.371
CAS #	2417296-84-3
PubChem CID	146161288
Appearance	Light yellow to yellow solid powder
LogP	3.1
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	18
Rotatable Bond Count	22
Heavy Atom Count	71
Complexity	1950
Defined Atom Stereocenter Count	0
SMILES	S(C([H])([H])C([H])([H])C([H])([H])[H])(N([H])C1C([H])=C([H])C(=C(C=1F)N1C([H])=C(C2=C([H])N=C([H])N=C2[H])C2=C1C([H])=C([H])C(=N2)N(C([H])([H])[H])C1([H])C([H])([H])C([H])([H])N(C(C([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])N([H])C2=C([H])C([H])=C([H])C3C(N(C(C=32)=O)C2([H])C(N([H])C(C([H])([H])C2([H])[H])=O)=O)=O)=O)C([H])([H])C1([H])[H])F)(=O)=O
InChi Key	FMUGAZVOOIUFAT-UHFFFAOYSA-N
InChi Code	InChI=1S/C48H54F2N10O10S/c1-3-25-71(66,67)56-36-8-7-34(49)45(43(36)50)59-28-33(30-26-51-29-52-27-30)44-37(59)9-11-39(54-44)57(2)31-13-17-58(18-14-31)41(62)15-19-68-21-23-70-24-22-69-20-16-53-35-6-4-5-32-42(35)48(65)60(47(32)64)38-10-12-40(61)55-46(38)63/h4-9,11,26-29,31,38,53,56H,3,10,12-25H2,1-2H3,(H,55,61,63)
Chemical Name	N-[3-[5-[[1-[3-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]propanoyl]piperidin-4-yl]-methylamino]-3-pyrimidin-5-ylpyrrolo[3,2-b]pyridin-1-yl]-2,4-difluorophenyl]propane-1-sulfonamide
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

ln Vitro	PROTAC BRAF-V600E degrader-1 (Compound 23)(1 nM-10 μM; 72 hours) decreases the viability of A375 and HT-29 cells [1]. In A375 cells, PROTAC BRAF-V600E degrader-1 (1–1000 nM; 16 hours or 0–24 hours) suppresses the expression of p-ERK and BRAF-V600E [1].
Cell Assay	Cell viability assay [1] Cell Types: A375 and HT-29 Tested Concentrations: 1 nM-10 μM Incubation Duration: 72 h Experimental Results: Inhibited cell viability of A375 and HT-29, IC50 were 46.5 nM and 51 nM respectively. Western Blot Analysis[1] Cell Types: A375 Tested Concentrations: 1, 4, 12, 37, 111, 333 and 1000 nM Incubation Duration: 16 hrs (hours) or 0-24 hrs (hours) Experimental Results: diminished induced ERK phosphorylation. Inhibits p-ERK and BRAF-V600E in a dose- and time-dependent manner.
References	[1]. Discovery of Selective Small Molecule Degraders of BRAF-V600E. J Med Chem. 2020 Apr 23;63(8):4069-4080.

Solubility Data

Solubility (In Vitro)

DMSO : ~170 mg/mL (~169.82 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	0.9989 mL	4.9947 mL	9.9893 mL
	5 mM	0.1998 mL	0.9989 mL	1.9979 mL
	10 mM	0.0999 mL	0.4995 mL	0.9989 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.