A CAE/COL-type 2,2'-bipyridine analog, COL H, was tested for neuroprotective activity in an in vivo zebrafish model of oxidative stress. The treatment with 1 µM COL H reduced the appearance of apoptotic cells by approximately 60%. [1]
In a parallel experiment, 1 µM COL A treatment in the same zebrafish model reduced the apoptosis rate by 44%. [1]
COL H was evaluated for cytotoxic activity against tumor cell lines A549, HCT116, and MDA-MB-231. The half-maximal inhibitory concentration (IC₅₀) values against all three cell lines were reported to be higher than 100 µM, indicating weak cytotoxic activity. [1]
Several CAE analogs (cyanogriside E, F, G, H) were tested for cytotoxic effects on various human cancer cell lines. Cyanogriside F and G showed cytotoxicity against HCT116 and HL-60 cells with IC₅₀ values of 0.8/3.6 µM and 3.1/2.0 µM, respectively. Cyanogriside E and H were cytotoxic against K562 cells with IC₅₀ values of 6.0 µM and 0.8 µM, respectively. [1]

2,2'-Bipyridyl (40 mg/kg; sc; once) causes a temporary hypotension within 24 hours of a hypertensive hyperglycemia (53.8 mg/100 mL rise over 2 hours) without leading to long-term diabetes [2].

The neuroprotective effect of COL H was assessed in an in vivo zebrafish model. Zebrafish were treated with COL H at a concentration of 1 µM, and the reduction in the appearance of apoptotic cells was quantified as a measure of neuroprotection against oxidative stress. [1]
For cytotoxic activity assays, tumor cell lines (A549, HCT116, MDA-MB-231, HCT116, HL-60, K562) were treated with various CAE/COL-type 2,2'-bipyridine compounds (e.g., COL H, cyanogrisides E-H). Cell viability was measured, and the half-maximal inhibitory concentration (IC₅₀) values were calculated to determine the potency of cytotoxic effects. [1]

Animal/Disease Models: Male Holtzman rat (6-8 weeks old)[2].
Doses: 40 mg/kg
Route of Administration: subcutaneous injection; once.
Experimental Results: Displayed hyperglycemic activity.

Absorption, Distribution and Excretion
Pyridine and its alkyl derivatives can be absorbed via the gastrointestinal tract, peritoneum, and lungs. Peritoneal absorption appears to be only slightly faster and more complete than gastrointestinal absorption… Generally, these bases can be rapidly absorbed through intact skin. /Pyridine Alkyl Derivatives/

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Metabolism/Metabolites 2,2'-Bipyridine inhibited aromatic hydroxylation in microsomes of 3-methylcholanthrene-treated rats and enhanced this process in microsomes of sodium phenobarbital-treated rats. 2,2'-Bipyridine produced a type I binding profile with the aerobic microsome components of sodium phenobarbital-treated rats and a type II binding profile with microsomes of 3-methylcholanthrene-treated rats.

Interactions
Concentrations of 2,2'-bipyridine at levels of 1.0–5.0 mmol significantly enhanced the covalent binding of (14)C-labeled carbon tetrachloride to rat liver microsomes. The biotransformation of M-fluorotyrosine via the hepatic tyrosine metabolic pathway plays a crucial role in M-fluorotyrosine-induced seizures in mice. Simultaneous administration of M-fluorotyrosine and α,α-bipyridine prevented M-fluorotyrosine-induced seizures. Non-human Toxicity Values Oral LD50 in rats: 256 mg/kg Subcutaneous LD50 in rats: 155 mg/kg Oral LD50 in rats: 100 mg/kg Intraperitoneal LD50 in rats: 150 mg/kg For more complete non-human toxicity data on 2,2'-bipyridine (6 values), please visit the HSDB record page.

[1]. Discovery of caerulomycin/collismycin-type 2,2'-bipyridine natural products in the genomic era. J Ind Microbiol Biotechnol. 2019;46(3-4):459-468.

[2]. The hyperglycemic activity of 2, 2'-bipyridine. Journal of Pharmacology and Experimental Therapeutics, 1962, 135(3): 317-322.

2,2'-Bipyridine is a bipyridine in which two pyridine rings are linked by a bond between the C-2 and C-2' positions. It acts as an inhibitor of ferroptosis and a chelating agent. 2,2'-Bipyridine has been reported in Dichilus gracilis, Dichilus lebeckioides, and other organisms with relevant data. It is a reagent used for iron determination. Mechanism of Action The mechanism of action of 2,2'-bipyridine (an iron (+2) chelating agent and platelet aggregation inhibitor) on platelets was investigated. At the low concentrations required to inhibit arachidonic acid-mediated aggregation, 2,2'-bipyridine and 4,4'-bipyridine-2HCl inhibited platelet cyclooxygenase. The mechanism by which ADP-induced aggregation is inhibited is that 2,2'-dipyridine does not alter the cell ultrastructure, serotonin or nucleotide content, nor does it interfere with the release of arachidonic acid-(14)C or the movement of calcium. Obviously, the low concentrations of these compounds inhibit cyclooxygenase not due to bidentate iron chelation, since the inhibitory effect of 4,4'-dipyridine is almost as good as that of 2,2'-dipyridine, but rather due to the binding of these inhibitors to the iron atom in the cyclooxygenase heme. The core chemical skeleton of the natural products CAE (kalumycin) and COL (colismycin) is a 2,2'-bipyridine (2,2'-BP) heterocyclic compound. They are a class of microbial natural products. [1] This review discusses strategies for discovering new members of the CAE/COL type 2,2'-bipyridine family, including conventional isolation methods, biosynthetic pathway engineering and bioinformatics-guided genome mining. [1]
Biosynthetic studies have elucidated the genetic basis and enzymatic steps for constructing the 2,2'-bipyridine backbone, which involves a hybrid polyketide synthase-nonribosomal peptide synthase (PKS-NRPS) assembly line. [1]
By engineering modifications to the biosynthetic pathway (e.g., through gene inactivation), a variety of novel COL analogs (e.g., COL SN, SC, C, DH, H, DA, D, DN, DS, H1-H5) and CAE analogs (e.g., cyanogenic glycosides EG, H) have been generated, expanding structural diversity. [1]
Collagen H (COL H) is one of the intermediates/analogs in this pathway and has been shown to have potential neuroprotective activity. [1]
Several synthetic calcimycin A (CAE) analogs have been patented for use as immunosuppressants; collagen (COL) derivatives have been patented for use as oxidative stress inhibitors, suggesting a broader therapeutic potential than the specific activities described herein. [1]

C10H8N2

156.1839

156.068

366-18-7

1474

White to off-white solid powder

1.1±0.1 g/cm3

272.5±0.0 °C at 760 mmHg

70-73 °C(lit.)

107.2±12.0 °C

0.0±0.5 mmHg at 25°C

1.581

1.28

0

2

1

12

120

0

ROFVEXUMMXZLPA-UHFFFAOYSA-N

InChI=1S/C10H8N2/c1-3-7-11-9(5-1)10-6-2-4-8-12-10/h1-8H

2-pyridin-2-ylpyridine

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 : ~100 mg/mL (~640.29 mM)

Solubility in Formulation 1: ≥ 3 mg/mL (19.21 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 30.0 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.

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Solubility in Formulation 2: ≥ 3 mg/mL (19.21 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 30.0 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.

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Solubility in Formulation 3: ≥ 3 mg/mL (19.21 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 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)