NPASS Compound

Natural Product: NPC321692

Natural Product ID	NPC321692
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	XXDDQPLHHUHJOU-IDTAVKCVSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11061531
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0002105] Glycosyl compounds [CHEMONTID:0002203] Glycosylamines

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 49 52 0 0 0 0 0 0 0 0999 V2000 -4.7140 -0.8380 -0.8119 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0168 -0.9719 -1.5791 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0865 -0.7336 -0.7243 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1711 0.6153 -0.4205 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7707 1.1770 -0.2768 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8977 0.1358 0.2281 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.4163 0.7627 0.8695 P 0 0 0 0 0 0 0 0 0 0 0 0 -3.2139 2.1956 0.3962 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4173 0.7870 2.5670 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0876 -0.1496 0.3843 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9543 0.1991 1.0878 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2167 -0.6313 0.6337 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6261 -0.3049 -0.7903 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0126 -0.9073 -0.8410 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3589 -1.0288 0.6255 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3877 -0.3123 1.3195 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6817 -0.5140 0.8891 N 0 0 0 0 0 0 0 0 0 0 0 0 4.1054 0.0845 2.0064 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4141 0.4303 1.8778 N 0 0 0 0 0 0 0 0 0 0 0 0 5.8297 0.0473 0.6628 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0522 0.1595 0.0403 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1566 -0.3321 -1.2069 N 0 0 0 0 0 0 0 0 0 0 0 0 6.1179 -0.9115 -1.8312 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9336 -1.0136 -1.2125 N 0 0 0 0 0 0 0 0 0 0 0 0 4.7241 -0.5498 0.0452 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1999 0.7541 0.6215 N 0 0 0 0 0 0 0 0 0 0 0 0 2.0115 -2.1714 -1.3975 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7468 1.0689 -0.9048 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4532 -1.8347 -0.3622 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9399 -0.5430 -1.5203 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0307 -0.2862 -2.4371 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1097 -2.0168 -1.9640 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7800 0.7781 0.4859 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7154 1.1602 -1.2461 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4633 1.5207 -1.2882 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7801 2.0539 0.3888 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1181 0.1814 2.9438 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1277 -0.0429 2.1565 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7254 1.2589 1.0010 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0287 -1.7089 0.6755 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0538 -0.7467 -1.5392 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6967 -0.2095 -1.3691 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2532 -2.0960 0.9725 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5286 0.2736 2.8768 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2195 -1.2992 -2.8288 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7718 0.1907 1.3046 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5183 1.7146 0.4185 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0754 -2.9000 -0.7299 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3762 1.3619 -0.1970 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 7 9 1 0 7 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 15 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 21 26 1 0 14 27 1 0 13 28 1 0 6 1 1 0 16 12 1 0 25 17 1 0 25 20 1 0 1 29 1 0 1 30 1 0 2 31 1 0 2 32 1 0 4 33 1 0 4 34 1 0 5 35 1 0 5 36 1 0 9 37 1 0 11 38 1 0 11 39 1 0 12 40 1 0 13 41 1 0 14 42 1 0 15 43 1 0 18 44 1 0 23 45 1 0 26 46 1 0 26 47 1 0 27 48 1 0 28 49 1 0 M END

Standard InCHIKey	XXDDQPLHHUHJOU-IDTAVKCVSA-N
Standard InCHI	InChI=1S/C14H21N6O7P/c15-12-9-13(17-6-16-12)20(7-18-9)14-11(22)10(21)8(27-14)5-26-28(23,24)19-1-3-25-4-2-19/h6-8,10-11,14,21-22H,1-5H2,(H,23,24)(H2,15,16,17)/t8-,10-,11-,14-/m1/s1
SMILES	C1COCCN1P(=O)(O)OCC2C(C(C(O2)N3C=NC4=C(N=CN=C43)N)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	416.12	Volume:	353.268 ? Van der Waals volume.
Dense:	1.178	LogP:	-1.716 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.181 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.613 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	22.0
TPSA:	178.31 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.414	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.253	Fsp³:	0.643
MCE-18:	88.696 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.017	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.037 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.032 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.036	Promiscuous compounds:	0.043

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.075	MDCK Permeability:	-5.324
Pgp-inhibitor:	0.0	Pgp-substrate:	0.05
PAMPA:	0.994 ? 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):	0.615
20% Bioavailability (F20%):	0.007	30% Bioavailability (F30%):	0.433
50% Bioavailability (F50%):	0.172

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.715
Plasma Protein Binding (PPB):	14.117%	Volume Distribution (VD):	-0.442
Fu:	84.973% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.888
OATP1B3 inhibitor:	0.99	BCRP inhibitor:	0.0
BSEP inhibitor:	0.019

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.011	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.004
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):

6.219

Half-life (T1/2):

1.716

ADMET: Toxicity

hERG Blockers:	0.016	hERG Blockers (10um):	0.051
Human Hepatotoxicity (H-HT):	0.663	Drug-induced Liver Injury (DILI):	0.913
AMES Toxicity:	0.517	Rat Oral Acute Toxicity:	0.223
Maximum Recommended Daily Dose:	0.829	Skin Sensitization:	0.193
Carcinogencity:	0.968	Eye Corrosion:	0.0
Eye Irritation:	0.363	Respiratory Toxicity:	0.716
Drug-induced Neurotoxicity:	0.983	Ototoxicity:	0.863
Hematotoxicity:	0.159	Drug-induced Nephrotoxicity:	0.997
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.091
A549 Cytotoxicity:	0.007	Hek293 Cytotoxicity:	0.317
BCF:	0.031 ? 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:	2.244 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.837 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.262 ? 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
NPO30193	Mycoplasma genitalium	Species	Mycoplasmataceae	Bacteria	n.a.	n.a.	n.a.	PMID[22817898]
NPO30193	Mycoplasma genitalium	Species	Mycoplasmataceae	Bacteria	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 NPC321692 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	24966
0.1-0.2	24718
0.2-0.3	60
0.3-0.4	47
0.4-0.5	31
0.5-0.6	18
0.6-0.7	15
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.7183	Intermediate Similarity	NPC185991
0.7183	Intermediate Similarity	NPC321814
0.7083	Intermediate Similarity	NPC328479
0.6957	Remote Similarity	NPC136349
0.6957	Remote Similarity	NPC219313
0.68	Remote Similarity	NPC324198
0.68	Remote Similarity	NPC326529
0.68	Remote Similarity	NPC319100
0.6711	Remote Similarity	NPC130586
0.6623	Remote Similarity	NPC324484
0.6538	Remote Similarity	NPC174802
0.6456	Remote Similarity	NPC606410
0.6375	Remote Similarity	NPC316618
0.6375	Remote Similarity	NPC323091
0.6	Remote Similarity	NPC156461
0.6	Remote Similarity	NPC107374
0.6	Remote Similarity	NPC600382
0.6	Remote Similarity	NPC612067
0.5942	Remote Similarity	NPC317821
0.5833	Remote Similarity	NPC484199
0.5765	Remote Similarity	NPC484196
0.5375	Remote Similarity	NPC121222
0.5366	Remote Similarity	NPC195140
0.5309	Remote Similarity	NPC472816
0.5309	Remote Similarity	NPC164952
0.5309	Remote Similarity	NPC600171
0.53	Remote Similarity	NPC90902
0.5294	Remote Similarity	NPC481375
0.527	Remote Similarity	NPC229974
0.5244	Remote Similarity	NPC302778
0.5244	Remote Similarity	NPC329404
0.5244	Remote Similarity	NPC212551
0.5204	Remote Similarity	NPC21461
0.519	Remote Similarity	NPC85689
0.5116	Remote Similarity	NPC325906
0.5116	Remote Similarity	NPC606116

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC321692 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4875
0.1-0.2	4125
0.2-0.3	72
0.3-0.4	45
0.4-0.5	21
0.5-0.6	4
0.6-0.7	6
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.7183	Intermediate Similarity	NPD283	Phase 4
0.6957	Remote Similarity	NPD548	Clinical (unspecified phase)
0.6538	Remote Similarity	NPD339	Phase 2
0.6533	Remote Similarity	NPD4171	Clinical (unspecified phase)
0.6364	Remote Similarity	NPD338	Approved
0.6	Remote Similarity	NPD249	Phase 4
0.6	Remote Similarity	NPD250	Phase 4
0.5309	Remote Similarity	NPD242	Phase 4
0.53	Remote Similarity	NPD4716	Approved
0.5172	Remote Similarity	NPD1776	Approved
0.5116	Remote Similarity	NPD1777	Phase 4

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