NPASS Compound

Natural Product: NPC578663

Natural Product ID	NPC578663
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{R},3~{R},4~{R},5~{S})-2-(6-aminopurin-9-yl)-5-[[[(2~{R},3~{S},4~{S},5~{S})-5-(6-aminopurin-9-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl]methyldisulfanyl]methyl]tetrahydrofuran-3,4-diol
IUPAC Name	(2~{R},3~{R},4~{R},5~{S})-2-(6-aminopurin-9-yl)-5-[[[(2~{R},3~{S},4~{S},5~{S})-5-(6-aminopurin-9-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl]methyldisulfanyl]methyl]tetrahydrofuran-3,4-diol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 62 67 0 0 0 0 0 0 0 0999 V2000 8.9146 3.0535 -0.8161 N 0 0 0 0 0 0 0 0 0 0 0 0 8.1728 1.9628 -1.3229 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3122 1.4937 -2.5808 N 0 0 0 0 0 0 0 0 0 0 0 0 7.5694 0.4519 -2.9886 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6854 -0.1486 -2.1901 N 0 0 0 0 0 0 0 0 0 0 0 0 6.4892 0.2668 -0.9106 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2581 1.3388 -0.5014 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8947 1.5687 0.7852 N 0 0 0 0 0 0 0 0 0 0 0 0 5.9528 0.6847 1.1464 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7026 -0.1175 0.1026 N 0 0 0 0 0 0 0 0 0 0 0 0 4.7581 -1.2068 0.0589 C 0 0 2 0 0 0 0 0 0 0 0 0 3.6129 -0.9187 -0.6284 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5116 -1.1006 0.1612 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6110 0.1146 0.1902 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9840 0.5729 -1.4084 S 0 0 0 0 0 0 0 0 0 0 0 0 -0.3155 -0.7937 -2.2730 S 0 0 0 0 0 0 0 0 0 0 0 0 -2.0321 -0.6198 -1.9607 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5584 -0.8528 -0.5911 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9547 -0.6374 -0.7040 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3950 -0.6029 0.5924 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.7526 -0.1385 0.7242 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.2913 0.3682 1.8488 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5798 0.7071 1.6368 N 0 0 0 0 0 0 0 0 0 0 0 0 -7.8590 0.4102 0.3590 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0142 0.5519 -0.3709 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.1544 1.0966 0.2553 N 0 0 0 0 0 0 0 0 0 0 0 0 -8.9795 0.1564 -1.6507 N 0 0 0 0 0 0 0 0 0 0 0 0 -7.8684 -0.3588 -2.2094 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7430 -0.4921 -1.4820 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.7242 -0.1133 -0.2021 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4461 0.4058 1.2128 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3781 0.1239 2.5618 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1528 0.1008 0.4648 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5850 1.2522 -0.0656 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9831 -1.3389 1.5787 C 0 0 2 0 0 0 0 0 0 0 0 0 2.8731 -0.1839 2.3512 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4271 -1.7562 1.4041 C 0 0 1 0 0 0 0 0 0 0 0 0 4.5224 -3.1443 1.4671 O 0 0 0 0 0 0 0 0 0 0 0 0 8.7065 4.0060 -1.1605 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6550 2.9029 -0.1107 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7171 0.1122 -4.0050 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4897 0.6451 2.1164 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2768 -2.0348 -0.5094 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8936 -1.9759 -0.1436 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1734 0.9898 0.6168 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7844 -0.1209 0.8748 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5780 -1.3647 -2.6231 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4031 0.3656 -2.3915 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4481 -1.9207 -0.3047 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2923 -1.5906 1.0460 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7760 0.4971 2.8113 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.8304 1.6562 -0.3098 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3708 0.9756 1.2592 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8309 -0.6850 -3.2577 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7599 1.4416 1.0584 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4510 -0.0310 2.8821 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4983 -0.3583 1.2493 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2196 1.7026 -0.6446 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3964 -2.1186 2.0923 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8351 -0.4425 3.3068 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0796 -1.3644 2.2209 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9994 -3.4436 0.6538 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 25 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 20 31 1 0 31 32 1 0 31 33 1 0 33 34 1 0 13 35 1 0 35 36 1 0 35 37 1 0 37 38 1 0 7 2 1 0 37 11 1 0 10 6 1 0 33 18 1 0 30 21 1 0 30 24 1 0 1 39 1 0 1 40 1 0 4 41 1 0 9 42 1 0 11 43 1 6 13 44 1 6 14 45 1 0 14 46 1 0 17 47 1 0 17 48 1 0 18 49 1 1 20 50 1 1 22 51 1 0 26 52 1 0 26 53 1 0 28 54 1 0 31 55 1 1 32 56 1 0 33 57 1 1 34 58 1 0 35 59 1 1 36 60 1 0 37 61 1 1 38 62 1 0 M END

Standard InCHIKey	HYGRWPFOTXXMNB-NJNOBOSFSA-N
Standard InCHI	InChI=1S/C20H24N10O6S2/c21-15-9-17(25-3-23-15)29(5-27-9)19-13(33)11(31)7(35-19)1-37-38-2-8-12(32)14(34)20(36-8)30-6-28-10-16(22)24-4-26-18(10)30/h3-8,11-14,19-20,31-34H,1-2H2,(H2,21,23,25)(H2,22,24,26)/t7-,8+,11+,12-,13-,14+,19-,20+
SMILES	NC1=NC=NC2=C1N=CN2[C@@H]1O[C@H](CSSC[C@@H]2O[C@H](N3C=NC4=C(N)N=CN=C43)[C@@H](O)[C@@H]2O)[C@H](O)[C@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	564.13	Volume:	481.773 ? Van der Waals volume.
Dense:	1.171	LogP:	-1.282 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.627 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.49 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	30.0
TPSA:	238.62 ? Topological Polar Surface Area.	H-Bond Acceptor:	16.0
H-Bond Donor:	8.0	Rings:	6.0
Heavy Atoms:	18.0

MedChem Properties

QED Drug-Likeness Score:	0.11	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.773	Fsp³:	0.5
MCE-18:	120.133 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.189	Fluc inhibitor:	0.005 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.081 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.199 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.679	Promiscuous compounds:	0.494

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.837	MDCK Permeability:	-5.221
Pgp-inhibitor:	0.0	Pgp-substrate:	0.101
PAMPA:	0.999 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.994
20% Bioavailability (F20%):	0.037	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	0.9

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.756	MRP1:	0.01
Plasma Protein Binding (PPB):	40.323%	Volume Distribution (VD):	-0.057
Fu:	53.354% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.099
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.002
HLM stability:	0.001 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

5.751

Half-life (T1/2):

1.938

ADMET: Toxicity

hERG Blockers:	0.073	hERG Blockers (10um):	0.17
Human Hepatotoxicity (H-HT):	0.812	Drug-induced Liver Injury (DILI):	1.0
AMES Toxicity:	0.984	Rat Oral Acute Toxicity:	0.489
Maximum Recommended Daily Dose:	0.705	Skin Sensitization:	0.997
Carcinogencity:	0.393	Eye Corrosion:	0.0
Eye Irritation:	0.011	Respiratory Toxicity:	0.464
Drug-induced Neurotoxicity:	0.964	Ototoxicity:	0.941
Hematotoxicity:	0.971	Drug-induced Nephrotoxicity:	0.986
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.263
A549 Cytotoxicity:	0.891	Hek293 Cytotoxicity:	0.72
BCF:	0.223 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	2.809 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.625 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.651 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO14594	Trachycladus laevispirulifer	Species	Trachycladidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11374963]
NPO14594	Trachycladus laevispirulifer	Species	Trachycladidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC578663 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	39402
0.1-0.2	10270
0.2-0.3	68
0.3-0.4	38
0.4-0.5	33
0.5-0.6	25
0.6-0.7	11
0.7-0.8	4
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.807	Intermediate Similarity	NPC136349
0.807	Intermediate Similarity	NPC219313
0.75	Intermediate Similarity	NPC156461
0.75	Intermediate Similarity	NPC107374
0.75	Intermediate Similarity	NPC600382
0.75	Intermediate Similarity	NPC612067
0.7455	Intermediate Similarity	NPC317821
0.7419	Intermediate Similarity	NPC185991
0.7419	Intermediate Similarity	NPC321814
0.7302	Intermediate Similarity	NPC328479
0.7015	Intermediate Similarity	NPC324484
0.697	Remote Similarity	NPC324198
0.697	Remote Similarity	NPC326529
0.697	Remote Similarity	NPC319100
0.6866	Remote Similarity	NPC130586
0.6667	Remote Similarity	NPC174802
0.6571	Remote Similarity	NPC606410
0.6479	Remote Similarity	NPC316618
0.6479	Remote Similarity	NPC323091
0.6301	Remote Similarity	NPC484199
0.623	Remote Similarity	NPC229974
0.6216	Remote Similarity	NPC484196
0.589	Remote Similarity	NPC606116
0.5775	Remote Similarity	NPC195140
0.5714	Remote Similarity	NPC209525
0.5714	Remote Similarity	NPC161659
0.5676	Remote Similarity	NPC325906
0.5625	Remote Similarity	NPC609472
0.5588	Remote Similarity	NPC85689
0.5556	Remote Similarity	NPC33996
0.5538	Remote Similarity	NPC309832
0.5493	Remote Similarity	NPC164952
0.5417	Remote Similarity	NPC302778
0.5417	Remote Similarity	NPC329404
0.5417	Remote Similarity	NPC212551
0.5352	Remote Similarity	NPC121222
0.5278	Remote Similarity	NPC472816
0.5278	Remote Similarity	NPC600171
0.5231	Remote Similarity	NPC609036
0.5217	Remote Similarity	NPC605318
0.5211	Remote Similarity	NPC239737
0.5169	Remote Similarity	NPC21461
0.5152	Remote Similarity	NPC164665
0.5143	Remote Similarity	NPC211025
0.5075	Remote Similarity	NPC269827
0.5075	Remote Similarity	NPC189068
0.5065	Remote Similarity	NPC481375

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC578663 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7195
0.1-0.2	1798
0.2-0.3	77
0.3-0.4	40
0.4-0.5	24
0.5-0.6	9
0.6-0.7	2
0.7-0.8	4
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.807	Intermediate Similarity	NPD548	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD249	Phase 4
0.75	Intermediate Similarity	NPD250	Phase 4
0.7419	Intermediate Similarity	NPD283	Phase 4
0.7188	Intermediate Similarity	NPD4171	Clinical (unspecified phase)
0.697	Remote Similarity	NPD338	Approved
0.6667	Remote Similarity	NPD339	Phase 2
0.5676	Remote Similarity	NPD1777	Phase 4
0.5526	Remote Similarity	NPD1776	Approved
0.5303	Remote Similarity	NPD193	Phase 2
0.5278	Remote Similarity	NPD1369	Phase 2
0.5278	Remote Similarity	NPD242	Phase 4
0.5256	Remote Similarity	NPD1732	Phase 3
0.5152	Remote Similarity	NPD186	Phase 1
0.5075	Remote Similarity	NPD195	Approved
0.5068	Remote Similarity	NPD1750	Clinical (unspecified phase)

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data