PPACK TFA 

PPACK TFA is an orally active, selective molecular glue degrader targeting IKZF2. Through a molecular glue mechanism, PPACK TFA binds to CRBN, recruits IKZF2 to form a ternary complex, and promotes its ubiquitination and proteasomal degradation. This further converts inhibitory regulatory T cells (T_reg) into effector-like T cells, enhances CD8⁺ T cell responses, and modulates the T_eff:T_reg balance. PPACK TFA also increases the production of the inflammatory cytokine IL-2 and reduces the suppressive activity of T_reg. PPACK TFA can be used in cancer immunotherapy research, and exhibits a synergistic effect when combined with immune checkpoint inhibitors such as anti-PD1^[1][3].

PPACK TFA rapidly and completely degrades IKZF2, reduces the expression of CD25 and FOXP3 in inhibitory regulatory T cells (Treg), converts them into effector-like T cells, and simultaneously promotes the proliferation of effector T cells (Teff)^[1].

PPACK TFA promotes the production of inflammatory cytokines IL-2 and IFNγ, enhances CD8⁺ T cell responses, regulates the T_eff:T_reg balance, and exerts a selective degradation effect on IKZF2^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In humanized CRBN mouse models, PPACK TFA induces IKZF2 depletion and significantly inhibits MC38 tumor growth. When combined with anti-PD1 or anti-LAG3, PPACK TFA significantly improves animal survival and induces durable tumor regression compared with monotherapy with anti-PD1 or anti-LAG3^[2][3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

564.99

C₂₃H₃₂ClF₃N₆O₅

157379-44-7

Solid

White to off-white

{d-Phe}-Pro-{Arg-Chloromethylketone}

{d-Phe}-P-{Arg-Chloromethylketone}

O=C([C@H]1N(CCC1)C([C@H](N)CC2=CC=CC=C2)=O)N[C@@H](CCCNC(N)=N)C(CCl)=O.O=C(C(F)(F)F)O

Room temperature in continental US; may vary elsewhere.

Sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Huang Y, et al. PLX-4545, a selective IKZF2 degrader, reprograms suppressive Tregs leading to tumor growth inhibition and combination benefit with immune checkpoint therapy[J]. Cancer Research, 2025, 85(8_Supplement_1): 6380-6380.

  [2]. Chen Z, et al. Development of PVTX-405 as a potent and highly selective molecular glue degrader of IKZF2 for cancer immunotherapy. Nat Commun. 2025 May 1;16(1):4095.

  [3]. Zhang X, et al. Discovery of a Novel Series of iso-Indolinone-Based Glutarimides as Highly Efficacious and Selective IKZF2 Molecular Glue Degraders. J Med Chem. 2025 Sep 11;68(17):18230-18257.  [Content Brief]