DNA/RNA polymerases; Nucleic acid synthesis machinery：Tubercidin (7-deazaadenosine) acts as an adenosine analog, interfering with RNA and DNA synthesis by incorporating into nucleic acids and inhibiting nucleotide-dependent enzymes (no specific IC₅₀ or Ki values reported). [1]

The inhibitory impact of tubercidin (7-Deazaadenosine) (0-10 nM; 14 d) on erythroid human myeloid progenitor cells and bone marrow is dose-dependent. On CFU-GM and BFU-E cells, tubercidin's half-life (IC50) is 3.4 nM and 3.7 nM, respectively.

---

- Inhibition of nucleic acid synthesis：In Escherichia coli and mammalian cells, tubercidin (10–50 μg/ml) inhibits RNA synthesis by 70–80% and DNA synthesis by 50–60%, as measured by reduced incorporation of [³H]-uridine and [³H]-thymidine into nucleic acids. It also blocks protein synthesis indirectly by impairing RNA production. [1]
- Antiviral activity：Tubercidin exhibits antiviral activity against vaccinia virus and herpes simplex virus (HSV) in cell cultures, with minimal inhibitory concentrations (MIC) ranging from 0.1 to 1 μg/ml. It inhibits viral DNA replication without affecting host cell viability at these concentrations. [2]

Antischistosomal activity：In mice infected with Schistosoma mansoni, tubercidin (5 mg/kg, intraperitoneal) reduces worm burden by 60–70% when administered daily for 5 days. Co-administration with nitrobenzylthioinosine 5'-monophosphate (NBMPR-P) prevents host toxicity while preserving antiparasitic efficacy. [3]
In order to preserve the lethality of shell Tubercidin and enable a second iteration of the regimen, finally with 100%, Tubercidin (7-Deazaadenosine) (i.p. ; 5 mg/kg; 10 days) collaborates with NBMPR-P [3].

RNA polymerase inhibition assay： 1. E. coli RNA polymerase is incubated with DNA template, [³H]-UTP, and tubercidin (5–50 μg/ml) in reaction buffer. 2. After 30 minutes at 37°C, trichloroacetic acid (TCA) precipitation is used to measure [³H]-UTP incorporation into RNA. 3. Tubercidin reduces RNA polymerase activity by 50–70% at 20 μg/ml. [1]

Cytotoxicity assay [2]
Cell Types: human bone marrow progenitor cells
Tested Concentrations: 0-10nM
Incubation Duration: 14 days
Experimental Results: Dose-dependent inhibitory effect on CFU-GM and BFU-E.

---

Nucleic acid synthesis inhibition assay： 1. HeLa cells or E. coli are cultured in medium containing tubercidin (1–50 μg/ml) and [³H]-uridine (for RNA) or [³H]-thymidine (for DNA). 2. After 4 hours, cells are harvested, and TCA-insoluble radioactivity is measured. 3. At 50 μg/ml, tubercidin inhibits RNA synthesis by 70% and DNA synthesis by 50% in HeLa cells. [1]

Animal/Disease Models: Female CD1 mice[2]
Doses: 5 mg/kg
Route of Administration: intraperitoneal (ip) injection; ]. 5 mg/kg; 10 day
Experimental Results: Protect mice from tuberculin.

---

Schistosomiasis mouse model： 1. Mice are infected with Schistosoma mansoni cercariae. 2. Tubercidin (5 mg/kg) is dissolved in saline and administered intraperitoneally daily for 5 days, either alone or with NBMPR-P (10 mg/kg). 3. Worm burden is assessed by perfusion of mesenteric veins, and toxicity is monitored via weight loss and histopathological analysis of liver/kidney. [3]

Host toxicity: Tuberculin alone can cause weight loss (15-20% weight loss in mice at a dose of 5 mg/kg) and liver and kidney damage (hepatocyte vacuolation and renal tubular necrosis). The LD₅₀ in mice is approximately 10 mg/kg (intraperitoneal injection). [3] - Toxicity prevention: Combination with NBMPR-P can reduce mortality from 80% (tuberculin alone) to 10% and reduce organ damage. [3]

---

6245 rat oral LD50 16 mg/kg Lung, pleural or respiratory system: pleural effusion; gastrointestinal tract: other changes; lung, pleural or respiratory system: pleural effusion Cancer Research., 29(116), 1969 [PMID:5763972]
6245 rat intraperitoneal injection 1 mg/kg Lung, pleural or respiratory system: pleural effusion; gastrointestinal tract: peritonitis; liver: other changes, Cancer Research., 29(116), 1969 [PMID:5763972]
6245 mouse oral LD50 is 28320 μg/kg, National Cancer Institute Screening Program Data Summary, Developmental Therapy Program, January 1986
6245 mouse intraperitoneal injection LD50 is 6 mg/kg, Compounds for Basic Research, Vol. 2, No. 6 Partial, Antibiotics, Upjohn Research Laboratory Project, 2(6)(-), 1971
6245 Intravenous LD50 in mice was 45 mg/kg, Journal of Antibiotics, Series A, 10(201), 1957

[1]. On the mode of action of 7-deaza-adenosine (Tubercidin). Biochim Biophys Acta. 1967 Mar 29;138(1):10-25.

[2]. Antiviral activity of C-5 substituted tubercidin analogues. J Med Chem. 1984 Mar;27(3):285-92.

[3]. Prevention of tubercidin host toxicity by nitrobenzylthioinosine 5'-monophosphate for the treatment of schistosomiasis. Antimicrob Agents Chemother. 1989 Jun;33(6):824-7.

Tuberculin is an N-glycosylpyrrolopyrimidine compound with an adenosine structure, in which the carbon atoms on the five-membered ring not attached to the ribose portion are replaced. Tuberculin is produced by the culture medium of Streptomyces tubericidus. It possesses antitumor activity and is a bacterial metabolite and antimetabolite. It is an N-glycosylpyrrolopyrimidine compound, belonging to the ribonucleoside class, and is also an antibiotic and antifungal agent. It is a purine ribonucleoside antibiotic that readily substitutes for adenosine in biological systems, but its incorporation into DNA and RNA inhibits the metabolism of these nucleic acids. Tuberculin has been reported in Plectonema radiosum, Actinopolyspora erythraea, and other organisms with relevant data. Tuberculin is an antibiotic and adenosine analogue isolated from Streptomyces tubericidus, possessing potential antitumor activity. Tuberculin can be incorporated into DNA and inhibit polymerase, thereby inhibiting DNA replication and the synthesis of RNA and proteins. The compound also possesses antifungal and antiviral activity. (NCI04)
A purine ribonucleoside antibiotic that readily replaces adenosine in biological systems, but its incorporation into DNA and RNA inhibits the metabolism of these nucleic acids.

---

Pyrrolo[2,3-d]pyrimidine nucleoside antibiotics tuberculin, toicamycin, and sangimycin, and their synthetic analogues 5-chloro-, 5,6-dichloro-, 5-bromo-, 6-bromo-, 5,6-dibromo-, 5-iodo-, 5-(1-hydroxyethyl)-, 5-(1-methoxyethyl)-, (E)-5-(2-bromovinyl)-, (E)-5-(2-cyanovinyl)-, 5-(2-buten-1-yl)-, 5-(3-hydroxypropyl)-, and 5-butyl tuberculin were evaluated. In HeLa cells, primary rabbit kidney cells, and Vero cell cultures, we tested the antiviral activity of these derivatives against six RNA viruses and three DNA viruses. Most derivatives showed significant activity against RNA viruses, with 6-bromo-, 5,6-dichloro-, and 5,6-dibromotuberculin exhibiting the lowest activity. The C-5 substituted derivatives were highly toxic to host cells. 5-(1-hydroxyethyl), 5-(1-methoxyethyl), and 5-(2-buten-1-yl)tuberculin showed higher selectivity against reovirus type 1, parainfluenza virus type 3, and Coxsackievirus B4 than tuberculin and 5-halogenated tuberculin. In in vivo anti-Coxsackie B4 virus infection activity tests in neonatal NMRI mice, 5-(1-hydroxyethyl) and 5-(1-methoxyethyl)tuberculin significantly reduced mortality at a dose of 100 μg per mouse. Meanwhile, its inhibitory effect on the growth of L-1210 cells was determined, and tocamycin (ID50 = 0.006 μg/mL) showed the strongest activity. This study shows the importance of C-5 structural modification and the potential of tuberculin C-5 substitution analogues as bioactive drugs. [1]

---

In this study, the host toxicity of the dosing regimen of tuberculin (7-deadenosine) combined with nitrobenzylthioinosine 5'-monophosphate (NBMPR-P) for the combined treatment of schistosomiasis was investigated in mice and in human bone marrow progenitor cells (MH el Kouni, D. Diop and S. Cha, Proceedings of the National Academy of Sciences 80:6667-6670, 1983; MH el Kouni, NJ Messier and S. Cha, Biochemical Pharmacology 36:3815-3821, 1987). Intraperitoneal injection of tuberculin (5 mg/kg/day) for four consecutive days resulted in 100% mortality in mice within 3 to 5 days after the first injection, accompanied by severe peritonitis and intestinal obstruction secondary to peritoneal adhesions. Daily administration of NBMPR-P (25 mg/kg) protected mice from the lethal effects of tuberculin and allowed for repeated treatment until sacrifice 22 days after the first injection, with a 100% survival rate. Blood chemistry, hematology, and histological examinations revealed no signs of damage to the liver, kidneys, spleen, pancreas, mesentery, or peritoneal mesothelial cells. In vitro experiments showed that tuberculin alone had a dose-dependent direct inhibitory effect on human bone marrow myeloid and erythroid progenitor cells, with inhibition rates of 50% for both granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst colony-forming units (BFU-E) at concentrations of 2–3 nM tuberculin. At high doses, BFU-E is more sensitive to tuberculin toxicity than CFU-GM. Complete inhibition of BFU-E colonies (99%) is achieved at a tuberculin concentration of 10 nM, while complete inhibition of CFU-GM colonies requires a concentration of 100 nM. NBMPR-P at concentrations of 10 to 100 nM can protect CFU-GM and BFU-E from tuberculin toxicity in a dose-dependent manner. [2]

---

- Mechanism of action: Tuberculin is converted to 7-denitro-ATP, which is incorporated into RNA and DNA, leading to chain termination and inhibition of nucleic acid synthesis. It also inhibits adenosine kinase and other ATP-dependent enzymes. [1]
- Therapeutic use: Its antiviral (anti-poxvirus, anti-herpesvirus) and anti-schistosomiasis activities have been studied, but its clinical application is limited due to host toxicity. [2][3]

C11H14N4O4

266.25326

266.101

C, 49.62; H, 5.30; N, 21.04; O, 24.04

69-33-0

6245

White to off-white solid powder

1.9±0.1 g/cm3

648.8±55.0 °C at 760 mmHg

247-248 °C (decomp)

346.2±31.5 °C

0.0±2.0 mmHg at 25°C

1.834

-0.12

4

7

2

19

334

4

C1=CN(C2=NC=NC(=C21)N)[C@H]3[C@@H]([C@@H]([C@H](O3)CO)O)O

HDZZVAMISRMYHH-KCGFPETGSA-N

InChI=1S/C11H14N4O4/c12-9-5-1-2-15(10(5)14-4-13-9)11-8(18)7(17)6(3-16)19-11/h1-2,4,6-8,11,16-18H,3H2,(H2,12,13,14)/t6-,7-,8-,11-/m1/s1

(2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol

7-Deazaadenosine; Antibiotic XK 101-1; B 120121; tubercidin; 7-Deazaadenosine; Tubercidine; M351LCX45Y; U-10071; CHEBI:48267; NSC 56408 SKI 26,996; tubercidin; 7-Deazaadenosine; 69-33-0; Sparsomycin A; Tubercidine; Antibiotic XK 101-1; SKI 26,996; Sparsomycin A; TBC; Tubercidin; Tubercidine; U 10071; U-10071; U10071

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 30 mg/mL (~112.68 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.39 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 (9.39 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.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (9.39 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.)