Name: TL13-12
Brand: BOC Sciences
Price: 299 USD
Availability: MadeToOrder

Size

Price

Stock

Quantity

5 mg

$299

In stock

Purity

≥98%

Solubility

Soluble in DMSO

Appearance

Yellow Solid

Storage

Store at -20°C

Shipping

Room temperature in continental US; may vary elsewhere.

IUPACName

N-[2-[2-[2-[4-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-3-methoxyphenyl]piperazin-1-yl]ethoxy]ethoxy]ethyl]-2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]acetamide

Synonyms

TL 13-12; TL-13-12; Acetamide, N-[2-[2-[2-[4-[4-[[5-chloro-4-[[2-[(1-methylethyl)sulfonyl]phenyl]amino]-2-pyrimidinyl]amino]-3-methoxyphenyl]-1-piperazinyl]ethoxy]ethoxy]ethyl]-2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]-; N-(2-(2-(2-(4-(4-((5-Chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazin-1-yl)ethoxy)ethoxy)ethyl)-2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)acetamide

Density

1.4±0.1 g/cm3

InChI Key

WXNUIPVZMJMPNM-UHFFFAOYSA-N

InChI

InChI=1S/C45H53ClN10O10S/c1-28(2)67(62,63)37-10-5-4-8-33(37)50-41-31(46)26-49-45(53-41)51-32-12-11-29(25-36(32)64-3)55-18-16-54(17-19-55)20-22-66-24-23-65-21-15-47-39(58)27-48-34-9-6-7-30-40(34)44(61)56(43(30)60)35-13-14-38(57)52-42(35)59/h4-12,25-26,28,35,48H,13-24,27H2,1-3H3,(H,47,58)(H,52,57,59)(H2,49,50,51,53)

SMILES

COC1=C(C=CC(N2CCN(CC2)CCOCCOCCNC(CNC3=C4C(N(C(C4=CC=C3)=O)C5CCC(NC5=O)=O)=O)=O)=C1)NC6=NC=C(C(NC7=C(S(=O)(C(C)C)=O)C=CC=C7)=N6)Cl

Pub Chem ID

138108740

Mechanism

Target: TL13-12 selectively targets anaplastic lymphoma kinase for PROTAC-mediated degradation.

Binding site: Its ALK inhibitor moiety binds the ATP-competitive catalytic site of ALK.

Mechanism of action: TL13-12 is a cereblon-based ALK degrader composed of an ALK inhibitor connected to the CRBN ligand pomalidomide. By recruiting ALK into proximity with CRL4CRBN, TL13-12 promotes ubiquitination and proteasomal clearance of ALK protein in ALK-dependent cellular models. This degradation mechanism provides a tool for examining ALK protein dependence beyond kinase inhibition alone. TL13-12 is suitable for studying NPM-ALK or EML4-ALK signaling, degradation concentration-response behavior, pathway durability, and comparative effects of removing ALK protein versus inhibiting its catalytic function.

Applications

• PROTAC-Mediated Kinase Degradation: TL13-12 serves as a potent tool for selectively degrading kinases involved in signaling pathways. By facilitating the ubiquitination and subsequent proteasomal degradation of target kinases, this PROTAC enables researchers to dissect complex cellular processes and elucidate kinase-driven disease mechanisms.

• Targeted Oncoprotein Degradation: Utilizing TL13-12 allows for the precise degradation of oncoproteins, providing a strategic approach to investigate cancer biology. This application aids in understanding the role of specific oncoproteins in tumorigenesis and offers insights into potential therapeutic targets for drug-resistant cancers.

• PROTAC-Driven Epigenetic Modulation: TL13-12 is instrumental in the targeted degradation of epigenetic regulators, offering a novel method to study gene expression control. By selectively removing key epigenetic proteins, researchers can explore the dynamic regulation of chromatin structure and its impact on cellular differentiation and development.

• Ubiquitin-Proteasome System Exploration: With TL13-12, researchers can delve into the intricacies of the ubiquitin-proteasome system by observing the degradation of specific substrates. This application enhances the understanding of protein homeostasis mechanisms and their implications in various cellular dysfunctions.

1. Chemically induced degradation of anaplastic lymphoma kinase (ALK).

Powell, C.E., Gao, Y., Tan, L., Donovan, K.A., Nowak, R.P., Loehr, A., Bahcall, M., Fischer, E.S., Jänne, P.A., George, R.E. and Gray, N.S., 2018. Journal of medicinal chemistry, 61(9), pp.4249-4255.

We present the development of the first small molecule degraders that can induce anaplastic lymphoma kinase (ALK) degradation, including in non-small-cell lung cancer (NSCLC), anaplastic large-cell lymphoma (ALCL), and neuroblastoma (NB) cell lines. These degraders were developed through conjugation of known pyrimidine-based ALK inhibitors, TAE684 or LDK378, and the cereblon ligand pomalidomide. We demonstrate that in some cell types degrader potency is compromised by expression of drug transporter ABCB1. In addition, proteomic profiling demonstrated that these compounds also promote the degradation of additional kinases including PTK2 (FAK), Aurora A, FER, and RPS6KA1 (RSK1).

ConcentrationVolumeMass	1 mg	5 mg	10 mg
1 mM	1.04 mL	5.2 mL	10.4 mL
5 mM	0.21 mL	1.04 mL	2.08 mL
10 mM	0.1 mL	0.52 mL	1.04 mL
50 mM	0.02 mL	0.1 mL	0.21 mL

Stock concentration: *

Desired final volume: *

Desired concentration: *

* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂