N-tert-Butoxycarbonyl-trans-4-hydroxy-D-proline is a non-cleavable (non-degradable) ADC linker used to synthesize ADCs (antibody-drug conjugates). N-tert-Butoxycarbonyl-trans-4-hydroxy-D-proline is also a PROTAC (PROteolysis TArgeting Chimera) linker based on alkyl chain and may be utilized to prepare PROTAC molecules.

Physicochemical Properties

Molecular Formula	C10H17NO5
Molecular Weight	231.25
Exact Mass	231.11
CAS #	147266-92-0
PubChem CID	688615
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	390.9±42.0 °C at 760 mmHg
Melting Point	123ºC
Flash Point	190.2±27.9 °C
Vapour Pressure	0.0±2.0 mmHg at 25°C
Index of Refraction	1.531
LogP	-0.71
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	3
Heavy Atom Count	16
Complexity	296
Defined Atom Stereocenter Count	2
SMILES	O([H])[C@]1([H])C([H])([H])N(C(=O)OC(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])[C@@]([H])(C(=O)O[H])C1([H])[H]
InChi Key	BENKAPCDIOILGV-NKWVEPMBSA-N
InChi Code	InChI=1S/C10H17NO5/c1-10(2,3)16-9(15)11-5-6(12)4-7(11)8(13)14/h6-7,12H,4-5H2,1-3H3,(H,13,14)/t6-,7+/m0/s1
Chemical Name	(2R,4S)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid
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	Non-cleavable Linker
ln Vitro	ADC cytotoxins are connected to antibodies through an ADC connector to form ADCs [1]. Two distinct ligands, one for the E3 ubiquitin ligase and the other for the target protein, are present in PROTAC and are joined by a linker. PROTAC selectively degrades target proteins by means of the intracellular ubiquitin-proteasome system [2].
References	[1]. Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov. 2017;16(5):315-337. [2]. PROTACs: An Emerging Therapeutic Modality in Precision Medicine. Cell Chem Biol. 2020;27(8):998-985.

Solubility Data

Solubility (In Vitro)

DMSO : 100 mg/mL (432.43 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.81 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (10.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.3243 mL	21.6216 mL	43.2432 mL
	5 mM	0.8649 mL	4.3243 mL	8.6486 mL
	10 mM	0.4324 mL	2.1622 mL	4.3243 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.