Name: AVL-292
Brand: BOC Sciences
Price: 299 USD
Availability: MadeToOrder

Purity

98%

Appearance

white solid powder

Application

Protein Kinase Inhibitors

IUPACName

N-[3-[[5-fluoro-2-[4-(2-methoxyethoxy)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide

Synonyms

CC-292; CC292; CC 292; AVL292; AVL 292; spebrutinib

InChI Key

KXBDTLQSDKGAEB-UHFFFAOYSA-N

InChI

InChI=1S/C22H22FN5O3/c1-3-20(29)25-16-5-4-6-17(13-16)26-21-19(23)14-24-22(28-21)27-15-7-9-18(10-8-15)31-12-11-30-2/h3-10,13-14H,1,11-12H2,2H3,(H,25,29)(H2,24,26,27,28)

SMILES

COCCOC1=CC=C(C=C1)NC2=NC=C(C(=N2)NC3=CC(=CC=C3)NC(=O)C=C)F

Mechanism

Target: AVL-292, also known as spebrutinib, targets BTK as a covalent kinase inhibitor.

Mechanism of Action: AVL-292 can serve as a covalent BTK-recognition ligand for BTK-directed PROTAC construction. The AVL-292-derived portion is designed to engage BTK, while an attached linker presents an E3 ligase ligand for recruitment of ubiquitin-ligase machinery. For degradation, covalent target engagement must be compatible with ternary-complex formation rather than preventing productive ligase proximity. When BTK, the PROTAC, and the E3 ligase form an appropriate complex, BTK can be ubiquitinated and subsequently degraded through the ubiquitin-proteasome system. This establishes a testable protein-depletion mechanism for research assays.

Applications

• E3 Ligase Recruitment Optimization: AVL-292 can be used as a PROTAC ligand to enable controlled recruitment of an E3 ubiquitin ligase to the target protein. Researchers can explore how AVL-292–based chimeras influence ternary complex formation, ubiquitination efficiency, and degradation kinetics across linker lengths and attachment sites.

• Targeted Degradation Profiling: AVL-292-derived PROTACs support systematic mapping of degradation potency and selectivity in cell-based assays. By varying PROTAC concentration and exposure time, investigators can quantify target protein loss, recovery after washout, and correlate degradation with ubiquitin–proteasome pathway engagement.

• Ternary Complex Mechanism Studies: AVL-292 can be applied to dissect the molecular basis of PROTAC activity by measuring ternary complex stability and cooperativity. Biophysical and cellular assays can evaluate whether AVL-292 promotes productive target–E3 assembly, guiding rational design for improved potency and reduced off-target degradation.

• Proteasome-Dependence Validation: AVL-292-containing PROTAC constructs can be used to confirm that observed protein reduction is driven by ubiquitin–proteasome degradation. Experiments using proteasome inhibition, ubiquitination perturbation, and rescue strategies help establish mechanism and distinguish degradation from transcriptional or translational effects.

1.Design and synthesis of sulfonamide-substituted diphenylpyrimidines (SFA-DPPYs) as potent Bruton's tyrosine kinase (BTK) inhibitors with improved activity toward B-cell lymphoblastic leukemia.

Liu H;Qu M;Xu L;Han X;Wang C;Shu X;Yao J;Liu K;Peng J;Li Y;Ma X Eur J Med Chem. 2017 Jul 28;135:60-69. doi: 10.1016/j.ejmech.2017.04.037. Epub 2017 Apr 14.

A new series of diphenylpyrimidine derivatives (SFA-DPPYs) were synthesized by introducing a functional sulfonamide into the C-2 aniline moiety of pyrimidine template, and then were biologically evaluated as potent Bruton's tyrosine kinase (BTK) inhibitors. Among these molecules, inhibitors 10c, 10i, 10j and 10k displayed high potency against the BTK enzyme, with IC;50; values of 1.18 nM, 0.92 nM, 0.42 nM and 1.05 nM, respectively. In particular, compound 10c could remarkably inhibit the proliferation of the B lymphoma cell lines at concentrations of 6.49 μM (Ramos cells) and 13.2 μM (Raji cells), and was stronger than the novel agent spebrutinib. In addition, the inhibitory potency toward the normal PBMC cells showed that inhibitor 10c possesses low cell cytotoxicity. All these explorations indicated that molecule 10c could serve as a valuable inhibitor for B-cell lymphoblastic leukemia treatment.

2.Structural optimization of diphenylpyrimidine derivatives (DPPYs) as potent Bruton's tyrosine kinase (BTK) inhibitors with improved activity toward B leukemia cell lines.

Zhao D;Huang S;Qu M;Wang C;Liu Z;Li Z;Peng J;Liu K;Li Y;Ma X;Shu X Eur J Med Chem. 2017 Jan 27;126:444-455. doi: 10.1016/j.ejmech.2016.11.047. Epub 2016 Nov 23.

A new series of diphenylpyrimidine derivatives (DPPYs) bearing various aniline side chains at the C-2 position of pyrimidine core were synthesized as potent BTK inhibitors. Most of these inhibitors displayed improved activity against B leukemia cell lines compared with lead compound spebrutinib. Subsequent studies showed that the peculiar inhibitor 7j, with IC;50; values of 10.5 μM against Ramos cells and 19.1 μM against Raji cells, also displayed slightly higher inhibitory ability than the novel agent ibrutinib. Moreover, compound 7j is not sensitive to normal cells PBMC, indicating low cell cytotoxicity. In addition, flow cytometry analysis indicated that 7j significantly induced the apoptosis of Ramos cells, and arrested the cell cycle at the G0/G1 phase. These explorations provided new clues to discover pyrimidine scaffold as more effective BTK inhibitors.

3.BTK inhibition is a potent approach to block IgE-mediated histamine release in human basophils.

Smiljkovic D;Blatt K;Stefanzl G;Dorofeeva Y;Skrabs C;Focke-Tejkl M;Sperr WR;Jaeger U;Valenta R;Valent P Allergy. 2017 Nov;72(11):1666-1676. doi: 10.1111/all.13166. Epub 2017 Apr 20.

BACKGROUND: ;Recent data suggest that Bruton's tyrosine kinase (BTK) is an emerging therapeutic target in IgE receptor (IgER)-cross-linked basophils.;METHODS: ;We examined the effects of four BTK inhibitors (ibrutinib, dasatinib, AVL-292, and CNX-774) on IgE-dependent activation and histamine release in blood basophils obtained from allergic patients (n=11) and nonallergic donors (n=5). In addition, we examined the effects of these drugs on the growth of the human basophil cell line KU812 and the human mast cell line HMC-1.;RESULTS: ;All four BTK blockers were found to inhibit anti-IgE-induced histamine release from basophils in nonallergic subjects and allergen-induced histamine liberation from basophils in allergic donors. Drug effects on allergen-induced histamine release were dose dependent, with IC;50; values ranging between 0.001 and 0.5 μmol/L, and the following rank order of potency: ibrutinib>AVL-292>dasatinib>CNX-774. The basophil-targeting effect of ibrutinib was confirmed by demonstrating that IgE-dependent histamine release in ex vivo blood basophils is largely suppressed in a leukemia patient treated with ibrutinib. Dasatinib and ibrutinib were also found to counteract anti-IgE-induced and allergen-induced upregulation of CD13, CD63, CD164, and CD203c on basophils, whereas AVL-292 and CNX-774 showed no significant effects.

ConcentrationVolumeMass	1 mg	5 mg	10 mg
1 mM	2.3616 mL	11.8080 mL	23.6161 mL
5 mM	0.4723 mL	2.3616 mL	4.7232 mL
10 mM	0.2362 mL	1.1808 mL	2.3616 mL
50 mM	0.0472 mL	0.2362 mL	0.4723 mL

AVL-292, also known as spebrutinib or CC-292, is a covalent BTK ligand containing an acrylamide electrophile. Its kinase-directed scaffold is relevant for BTK degrader design, where irreversible target engagement and linker placement must be evaluated carefully. This molecule is described in detail below.

Structure: The structure contains an anilinopyrimidine kinase-binding core, a fluoroaryl methoxyethoxy substituent, and an acrylamide attached through an anilide-like phenyl linker. The acrylamide is a Michael acceptor associated with covalent cysteine engagement.

Reactivity: In BTK PROTAC design, the acrylamide warhead should usually be preserved if covalent BTK engagement is desired, while linker extension should be explored from a solvent-tolerant aryl or alkoxy substituent rather than the electrophile itself. PEG or alkyl linkers can be connected to CRBN or VHL ligands, and reversible versus covalent BTK engagement should be compared experimentally because covalent occupancy may influence catalytic degradation turnover.

Do you have any information on its activity in vitro?

I have. AVL-292 less potently inhibits Yes, c-Src, Brk, Lyn, and Fyn with IC50s of 723 nM, 1.729 μM, 2.43 μM, 4.4 μM, and 7.15 μM, rspectively.

7/6/2016

Do you have any information on its activity in vivo?

In a mouse model of collagen-induced arthritis, AVL-292 dose-dependent inhibited the clinical symptoms of this type of inflammation, including the degree of swelling in the joints and PAWS and the reduction of redness in the affected PAWS.

21/11/2016

Please, Can you tell me the IC50 value of AVL-292?

Extensive analysis showed that the EC50 occupied by AVL-292 dose-responsive Btk in Ramos cells (EC50=6 nM) was directly related to the EC50 of cells in which AVL-292 inhibited Btk kinase (EC50=8 nM).

5/5/2017

We are looking for AVL-292, please tell me how AVL-292 inhibits the proliferation of B cells.

Hi, AVL-292 further inhibits the proliferation of B cells by inhibiting the activity of BTK with EC50 of 3 nM.

12/11/2019

We'd like to know that how AVL-292 inhibits the proliferation of B cells.

AVL-292 inhibits the proliferation of B cells by inhibiting the activity of BTK, with EC50 of 3 nM.

11/2/2022

inhibit B-cell proliferation

In vitro, AVL-292 significantly inhibited B-cell proliferation more potently than T-cell proliferation and reduced both lymphoid and myeloid cytokine production and degranulation, as well as osteoclastogenesis. Well done.

25/9/2016

inhibit anti-IgE-induced histamine release from basophils

In my research, AVL-292 significantly inhibits anti-IgE-induced histamine release from basophils in nonallergic subjects and allergen-induced histamine liberation from basophils in allergic tars. I’m very happy with the inhibitive effect.

17/3/2017

block the downstream BCR pathway

AVL-29 blocked the downstream BCR pathway with a dose-dependent EC50 of 8 nM. Happy with purchase.

28/4/2018

arrest clinical signs of inflammation

I'm so happy with the performance and results. AVL-292 arrested clinical signs of inflammation in a collagen-induced mouse model of arthritis, including a reduction in joint and paw swelling and visible redness in infected PAWS.

13/10/2018

reduce serum chemokines chemokine ligand 13

Our results revealed that AVL-292 significantly reduced serum chemokines chemokine ligand 13 (CXCL13), macrophage inflammatory protein-1β (MIP-1β), and the bone resorption biomarker carboxy-terminal collagen cross-linking telopeptide (CTX-I) (P < 0.05). Worked perfectly.

1/12/2021

inhibit Btk activity

The concentration at which AVL-292 inhibits 90% of Btk activity in Ramos cells is 35 nM while the concentration of AVL-292 required for 90% occupancy of Btk is 39 nM. Happy with purchase.

2/6/2022

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* 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