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Fig. 1 · Structure
Cat. No.
A11534
CAS No.
53910-25-1
Formula
C11H16N4O4
Mol. Weight
268.27

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Pentostatin

Cat. No. A11534 CAS 53910-25-1

Adenosine deaminase inhibitor

Pentostatin is an irreversible inhibitor of adenosine deaminase (Ki = 2.5 pM).

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Publications for Pentostatin

1 publication citing this product

  1. Lifang Han, .et al. , Cell Rep, 2022, May 31;39(9) PMID: 35649375
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Biological Activity

Bioactivity / Mechanism

Pentostatin inhibits adenosine deaminase (ADA). In a bovine spleen ADA assay using the fluorescent adenosine analogue tzA, it gave a reported IC50 of 1.44 ± 0.14 nM after 10 minutes. This value describes that assay and substrate, rather than a cellular treatment concentration. [1]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

In Vitro Studies

RNA from HEK cells exposed to pentostatin (0.3 μg/mL, 72 hours) induced more IFN-α in human PBMCs after protamine formulation than RNA from untreated cells. TNF-α induction was not significantly changed. The result concerns transferred cellular RNA and does not establish direct immune-receptor agonism by pentostatin. [2]

Inhibition of bovine spleen ADA in a fluorescent substrate assay

Biochemical assay · Bovine spleen adenosine deaminase; fluorescent isothiazolo[4,3-d]pyrimidine adenosine analogue (tzA) substrate [1]

Pentostatin inhibited conversion of tzA to tzI. The fitted IC50 was 1.44 ± 0.14 nM; the authors also calculated KI = 1.19 ± 0.15 nM using Cheng–Prusoff. These assay-derived values are not asserted as universal affinity constants.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
ADA-mediated conversion of tzA to tzI after 10 minutesIC50 1.44 ± 0.14 nM[1]
Author-calculated inhibition constant from fluorescent-substrate IC50KI (Cheng–Prusoff) 1.19 ± 0.15 nM[1]

Literature-Reported Treatment Conditions

Treatment concentration
Pentostatin series illustrated: 0, 0.1, 1, 2.5 and 10 nM; tzA 3.9 μM; ADA 4.1 mU/mL
Exposure duration
10-minute monitoring
Method
Fluorescence-based tzA-to-tzI conversion, excitation 322 nm and emission 410 nm; normalization to no-inhibitor conversion and sigmoidal Hill fitting.
Vehicle
50 mM phosphate buffer, pH 7.4; pentostatin-specific stock solvent not explicitly assigned in read text.
Reported limits
Assay temperature and pentostatin-specific stock preparation not established by read passages. SI not retrieved. Each inhibitor concentration was tested in triplicate; ± type not established.
Methods and source locations

Compound reported in the paper: Pentostatin; Compound label in the paper: Pentostatin

Evidence applies to the pentostatin tested in this paper; no Adooq lot identity, purity or performance validation is established.

Results and Discussion, inhibitor IC50 paragraph; Figure 4a,b,d and caption; Experimental Section, Henri-Michaelis-Menten Kinetics General Methods and Screening of Potential Inhibitors

ADA-mediated conversion of tzA to tzI after 10 minutes: Sigmoidal Hill fit; inhibitor concentrations tested in triplicate. Uninhibited conversion provides the normalization control; EHNA is a comparator. — Results and Discussion, inhibitor IC50 paragraph; Figure 4a,b,d and caption; Experimental Section, Henri-Michaelis-Menten Kinetics General Methods and Screening of Potential Inhibitors

Author-calculated inhibition constant from fluorescent-substrate IC50: Reported transformation of IC50 using Cheng–Prusoff; not an independently measured binding constant. ± definition not established in read passages. — Results and Discussion, inhibitor IC50 paragraph; Figure 4a,b,d and caption; Experimental Section, Henri-Michaelis-Menten Kinetics General Methods and Screening of Potential Inhibitors

RNA from pentostatin-treated cells increases IFN-α induction

Cell-based study · Human HEK cells as RNA source; human peripheral blood mononuclear cells (hPBMCs) as cytokine responders [2]

RNA isolated from pentostatin-treated HEK cells induced greater IFN-α release from hPBMCs after protamine formulation than RNA from untreated cells. TNF-α induction did not differ significantly. This is an RNA-transfer assay, not direct cytokine stimulation by pentostatin.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
IFN-α released by hPBMCs exposed to protamine-formulated RNA from treated versus untreated HEK cellsDirection and reported p value Increased IFN-α; p = 0.0390[2]
TNF-α released in the same RNA-transfer assayReported p value No significant difference; p = 0.3763[2]

Literature-Reported Treatment Conditions

Treatment concentration
HEK-cell pretreatment: 0.3 μg/mL pentostatin
Exposure duration
72-hour HEK treatment; responder incubation overnight in caption (24 hours in shared formulation method)
Method
Extracted total RNA was formulated with protamine and incubated with hPBMCs; supernatant cytokines quantified by ELISA.
Vehicle
Pentostatin prepared in PBS; control RNA from untreated HEK cells.
Co-treatment
Protamine formulation of extracted RNA for the downstream hPBMC assay; not co-treatment of HEK cells with a second drug.
Reported limits
Figure 1A–B specifies experimental duplicates, mean ± SD; independent donor/biological replicate count is not given in that caption.
Methods and source locations

Compound reported in the paper: Pentostatin; Compound label in the paper: Pentostatin

Evidence applies to the pentostatin tested in this paper; no Adooq lot identity, purity or performance validation is established.

Figure 1A–B and caption; Results and discussion, RNA-transfer paragraph; Materials and methods, Drugs, Protamine-RNA formulations and ELISAs

IFN-α released by hPBMCs exposed to protamine-formulated RNA from treated versus untreated HEK cells: Figure 1A, ELISA; experimental duplicates; mean ± SD; t test. No exact bar heights extracted. — Figure 1A–B and caption; Results and discussion, RNA-transfer paragraph; Materials and methods, Drugs, Protamine-RNA formulations and ELISAs

TNF-α released in the same RNA-transfer assay: Figure 1B, ELISA; experimental duplicates; mean ± SD; t test. No exact bar heights extracted. — Figure 1A–B and caption; Results and discussion, RNA-transfer paragraph; Materials and methods, Drugs, Protamine-RNA formulations and ELISAs

In Vivo Studies

In the MB49 mouse tumor model, a single intravenous dose of pentostatin (10 μg per mouse on day 6) reduced tumor growth in wild-type, TLR7-deficient and MAVS-deficient hosts, whereas TLR3-deficient hosts showed no treatment response. These findings support a host TLR3-dependent downstream effect in this model. [2]

Activity depended on tumor model and treatment context. In B16 melanoma-bearing mice, pentostatin alone did not significantly inhibit tumor growth. Combining pentostatin with anti-PD1 improved growth control relative to anti-PD1 alone, and only the combination extended survival in the reported comparison. [2]

Host TLR3 is required for growth control in the MB49 model

Animal study · Subcutaneous MB49 tumors in WT, TLR3-KO, TLR7-KO and MAVS-KO mice; knockouts on C57BL/6 background [2]

Pentostatin controlled MB49 tumor growth in WT, TLR7-KO and MAVS-KO hosts but did not distinguish treated from untreated TLR3-KO hosts. This supports host TLR3 dependence under these conditions; it does not demonstrate direct TLR3 binding.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Tumor-volume response to pentostatin within each host genotypeDirection and reported significance WT, TLR7-KO and MAVS-KO: reduced growth, p < 0.0001; TLR3-KO: no treatment response identified[2]
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
Pentostatin across WT and knockout genotypes
10 μg per mouse		Untreated mice within each genotypeGrowth control observed in WT, TLR7-KO and MAVS-KO groups; absent in TLR3-KO.[2]
Untreated genotype controlsPentostatin-treated mice of the same genotypeComparator for genotype-specific drug response.[2]
Pentostatin across WT and knockout genotypes
Model: MB49-bearing WT, TLR3-KO, TLR7-KO and MAVS-KO mice
Route: Intravenous
Frequency: Once
Treatment course: Day 6 after tumor implantation; growth assessed to day 10
Vehicle: PBS for pentostatin preparation
Reported limits: Caption gives genotype-group n: WT 7, TLR3-KO 7, TLR7-KO 6, MAVS-KO 7; separate treated/untreated allocation is not clarified.
Untreated genotype controls
Model: MB49-bearing WT, TLR3-KO, TLR7-KO and MAVS-KO mice
Treatment course: Tumor growth assessed from day 6 to day 10
Reported limits: No injection-matched vehicle group specified; n allocation ambiguity retained.
Methods and source locations

Compound reported in the paper: Pentostatin; Compound label in the paper: Pentostatin

Evidence applies to the pentostatin tested in this paper; no Adooq lot identity, purity or performance validation is established.

Figure 3A–B and caption; Results and discussion, knockout comparison; Materials and methods, Mice, Drugs and Tumor models and treatment

Tumor-volume response to pentostatin within each host genotype: Figure 3A, two-way ANOVA; mean ± SEM. Genotype n in caption: WT 7, TLR3-KO 7, TLR7-KO 6, MAVS-KO 7. Exact tumor volumes not digitized. — Figure 3A–B and caption; Results and discussion, knockout comparison; Materials and methods, Mice, Drugs and Tumor models and treatment

Pentostatin across WT and knockout genotypes · Figure 3A–B and caption; Results and discussion, knockout comparison; Materials and methods, Mice, Drugs and Tumor models and treatment

Untreated genotype controls · Figure 3A–B and caption; Results and discussion, knockout comparison; Materials and methods, Mice, Drugs and Tumor models and treatment

B16 melanoma limits monotherapy activity and supports combination benefit

Animal study · B16 tumors in WT C57BL/6 mice [2]

Pentostatin alone did not significantly delay B16 tumor growth. Anti-PD1 delayed growth, and combining it with pentostatin improved growth control versus anti-PD1 alone. Only the combination extended survival in the reported multi-group comparison; a formal pharmacologic synergy estimate was not supplied.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
B16 tumor-growth comparisonsReported p values Pentostatin vs untreated: p = 0.1758; anti-PD1 vs untreated: p = 0.0054; combination vs untreated: p < 0.0001; combination vs anti-PD1: p = 0.0464[2]
Overall survival in B16 tumor-bearing miceMulti-group survival comparison Only combination extended survival; p = 0.0081[2]
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
Pentostatin alone
10 μg per mouse		Untreated miceNo significant tumor-growth effect versus untreated (p = 0.1758).[2]
Anti-PD1 alone
Anti-PD1 100 μg per mouse per injection		Untreated mice and combination groupDelayed growth versus untreated (p = 0.0054); combination had greater growth inhibition.[2]
Pentostatin plus anti-PD1
Pentostatin 10 μg per mouse; anti-PD1 100 μg per mouse per injection		Untreated, pentostatin-alone and anti-PD1-alone groupsGreater growth inhibition than anti-PD1 alone (p = 0.0464); only combination extended survival in reported comparison.[2]
Untreated B16 controlsEach active treatment groupReference for growth and survival comparisons.[2]
Pentostatin alone
Model: B16 tumors in WT C57BL/6 mice
Route: Intravenous
Frequency: Once
Treatment course: Day 6
Vehicle: PBS for pentostatin preparation
Reported limits: n = 6 for this treated group.
Anti-PD1 alone
Model: B16 tumors in WT C57BL/6 mice
Route: Intravenous
Frequency: Two injections
Treatment course: Days 4 and 8
Reported limits: n = 6; antibody vehicle not specified in caption.
Pentostatin plus anti-PD1
Model: B16 tumors in WT C57BL/6 mice
Route: Intravenous
Frequency: Pentostatin once; anti-PD1 twice
Treatment course: Anti-PD1 days 4 and 8; pentostatin day 6
Vehicle: PBS for pentostatin preparation
Reported limits: n = 6; survival p = 0.0081 is a multi-group test, not a pairwise effect estimate.
Untreated B16 controls
Model: B16 tumors in WT C57BL/6 mice
Treatment course: Observed alongside treated groups
Reported limits: Untreated-group n is not explicitly stated in the Figure 4 caption.
Methods and source locations

Compound reported in the paper: Pentostatin; Compound label in the paper: Pentostatin

Evidence applies to the pentostatin tested in this paper; no Adooq lot identity, purity or performance validation is established.

Figure 4A–B and caption; Results and discussion, B16 combination paragraph; Materials and methods, Drugs, Mice and Tumor models and treatment

B16 tumor-growth comparisons: Figure 4A and caption; two-way ANOVA. No exact tumor volumes inferred from curves. — Figure 4A–B and caption; Results and discussion, B16 combination paragraph; Materials and methods, Drugs, Mice and Tumor models and treatment

Overall survival in B16 tumor-bearing mice: Figure 4B and caption; Mantel–Cox multi-group comparison, as reported. No median survival estimated. — Figure 4A–B and caption; Results and discussion, B16 combination paragraph; Materials and methods, Drugs, Mice and Tumor models and treatment

Pentostatin alone · Figure 4A–B and caption; Results and discussion, B16 combination paragraph; Materials and methods, Drugs, Mice and Tumor models and treatment

Anti-PD1 alone · Figure 4A–B and caption; Results and discussion, B16 combination paragraph; Materials and methods, Drugs, Mice and Tumor models and treatment

Pentostatin plus anti-PD1 · Figure 4A–B and caption; Results and discussion, B16 combination paragraph; Materials and methods, Drugs, Mice and Tumor models and treatment

Untreated B16 controls · Figure 4A–B and caption; Results and discussion, B16 combination paragraph; Materials and methods, Drugs, Mice and Tumor models and treatment

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 53910-25-1
Applications Adenosine deaminase inhibitor
Formula C11H16N4O4
Molecular Weight 268.27
Synonyms Deoxycoformycin
SMILES
C1C(C(OC1N2C=NC3=C2NC=NCC3O)CO)O

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO 49 mg/mL (182.64 mM)
Water 49 mg/mL (182.64 mM)
Ethanol Insoluble

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Paul T. Ludford III, Alexander R. Rovira, Andrea Fin, et al. Fluorescing Isofunctional Ribonucleosides: Assessing Adenosine Deaminase Activity and Inhibition ChemBioChem (2019). PMID: 30566279 DOI: 10.1002/cbic.201800665 Source material
  2. [2] Marina Tusup, Thomas M. Kündig, Steve Pascolo. Epitranscriptomics modifier pentostatin indirectly triggers Toll-like receptor 3 and can enhance immune infiltration in tumors Molecular Therapy (2022). PMID: 34563676 DOI: 10.1016/j.ymthe.2021.09.022 Source material

Publications

1 publication citing this product

  1. Lifang Han, .et al. , Cell Rep, 2022, May 31;39(9) PMID: 35649375

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