TD-165 is a CRBN degradation agent based on PROTAC technology. TD-165 includes a CRBN ligand binding group, a linker and a VHL binding group.

Physicochemical Properties

Molecular Formula	C46H59N7O8S
Molecular Weight	870.0678
Exact Mass	869.414
CAS #	2305936-56-3
PubChem CID	138574052
Appearance	White to yellow solid powder
LogP	6.5
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	20
Heavy Atom Count	62
Complexity	1620
Defined Atom Stereocenter Count	3
SMILES	S1C([H])=NC(C([H])([H])[H])=C1C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])N([H])C([C@]1([H])C([H])([H])[C@]([H])(C([H])([H])N1C([C@]([H])(C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])N([H])C(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C1=C([H])C([H])=C([H])C2C(N(C(C=21)=O)C1([H])C(N([H])C(C([H])([H])C1([H])[H])=O)=O)=O)=O)=O)O[H])=O
InChi Key	KSXVXTSIDVRZBR-IINAPWRYSA-N
InChi Code	InChI=1S/C46H59N7O8S/c1-28-39(62-27-49-28)30-19-17-29(18-20-30)25-48-41(57)35-24-31(54)26-52(35)45(61)40(46(2,3)4)50-36(55)16-11-9-7-5-6-8-10-12-23-47-33-15-13-14-32-38(33)44(60)53(43(32)59)34-21-22-37(56)51-42(34)58/h13-15,17-20,27,31,34-35,40,47,54H,5-12,16,21-26H2,1-4H3,(H,48,57)(H,50,55)(H,51,56,58)/t31-,34?,35+,40-/m1/s1
Chemical Name	(2S,4R)-1-[(2S)-2-[11-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]undecanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
Synonyms	TD165; TD 165
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 Note: This product requires protection from light (avoid light exposure) during transportation and storage.
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	TD-165 (0-100 nM; 24 hours) had 50% degradation concentration (DC50) and maximum degradation (Dmax) values of 20.4 nM and 99.6%, respectively[1]. In HEK293T cells, TD-165 (0.1-10 μM; 24 hours) decreases CRBN protein levels in a concentration-dependent manner [1].
Cell Assay	Cell Viability Assay[1] Cell Types: HEK293T cells Tested Concentrations: 0-100 nM Incubation Duration: 24 hrs (hours) Experimental Results: demonstrated an DC50 value of 20.4 nM. Western Blot Analysis[1] Cell Types: HEK293T cells Tested Concentrations: 0.1, 1, and 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: diminished the level of CRBN protein.
References	[1]. Disordered region of cereblon is required for efficient degradation by proteolysis-targeting chimera.Sci Rep. 2019 Dec 23;9(1):19654.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~57.47 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	1.1493 mL	5.7467 mL	11.4933 mL
	5 mM	0.2299 mL	1.1493 mL	2.2987 mL
	10 mM	0.1149 mL	0.5747 mL	1.1493 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.