NPASS Compound

Natural Product: NPC487214

Natural Product ID	NPC487214
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	RTRRNASIAZHUPE-JIGWJBEDSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	132526857
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0000507] Isoflavonoid O-glycosides

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 75 79 0 0 0 0 0 0 0 0999 V2000 -7.5400 -0.7566 -2.9749 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4087 0.0318 -2.0302 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.7824 -0.8740 -0.8740 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.0863 -0.0620 0.3722 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.7981 0.6356 0.7487 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.9241 0.8362 -0.4789 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.7132 1.1580 -1.5899 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0221 1.8468 -0.2008 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6436 1.7455 -0.2196 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8750 2.8824 0.1021 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5018 2.8395 0.0993 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8008 1.6926 -0.2153 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5683 0.5975 -0.5254 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9397 0.6108 -0.5306 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3575 1.5987 -0.2275 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4392 2.5788 -0.7738 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7492 2.4887 -0.7760 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3755 1.4400 -0.2475 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7440 1.3754 -0.2652 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4771 0.3027 0.2716 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7164 -0.6933 0.8245 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3301 -0.6801 0.8702 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6651 0.3959 0.3292 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2851 0.5111 0.3208 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3738 -0.4139 0.8321 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8390 0.3186 0.2123 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6596 -0.7101 0.7052 C 0 0 1 0 0 0 0 0 0 0 0 0 7.5050 -1.2105 -0.4449 C 0 0 1 0 0 0 0 0 0 0 0 0 8.8705 -0.5676 -0.3280 C 0 0 1 0 0 0 0 0 0 0 0 0 9.5004 -1.1617 0.9197 C 0 0 2 0 0 0 0 0 0 0 0 0 8.5487 -0.9704 2.0712 C 0 0 2 0 0 0 0 0 0 0 0 0 8.1646 -2.3323 2.6075 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4221 -0.2613 1.7844 O 0 0 0 0 0 0 0 0 0 0 0 0 10.6841 -0.4892 1.1894 O 0 0 0 0 0 0 0 0 0 0 0 0 9.6646 -0.8352 -1.4336 O 0 0 0 0 0 0 0 0 0 0 0 0 10.0383 0.3671 -2.0230 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5629 -2.5815 -0.4111 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1237 -0.1510 1.6557 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.4504 -0.8575 1.4378 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.6681 -0.4747 1.9973 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.9232 -1.5673 -1.2065 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.9679 -1.7477 -3.2224 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4284 -0.2070 -3.9509 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5198 -0.9139 -2.5951 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2986 0.3782 -2.6021 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9088 -1.5151 -0.6681 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.8351 0.7421 0.1515 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0526 1.6194 1.1917 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4262 -0.0979 -0.7044 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4418 3.7709 0.3458 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9198 3.7241 0.3481 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0717 -0.3359 -0.7818 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4750 -0.2847 -0.7840 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0113 3.4742 -1.2285 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3453 2.1722 -0.7058 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1917 -1.5674 1.2680 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7440 -1.4668 1.3065 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1084 -1.5902 1.0940 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0220 -0.8822 -1.3884 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7114 0.5150 -0.1597 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6537 -2.2325 0.7362 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0805 -0.4333 2.9119 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6683 -3.1542 2.0239 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4364 -2.4357 3.6938 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0779 -2.5331 2.5767 H 0 0 0 0 0 0 0 0 0 0 0 0 11.3509 -0.7897 0.5228 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6803 0.1747 -2.9203 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6011 0.9586 -1.2493 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1717 0.9453 -2.3964 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1416 -2.8923 -1.1721 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1821 0.2374 2.5870 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.8830 -1.1538 2.8364 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.4232 -0.5004 1.1898 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.5182 0.5594 2.4014 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3626 -1.1416 -1.9710 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 6 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 12 15 1 0 15 16 2 0 16 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 20 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 31 33 1 0 30 34 1 0 29 35 1 0 35 36 1 0 28 37 1 0 5 38 1 0 4 39 1 0 39 40 1 0 3 41 1 0 7 2 1 0 14 9 1 0 24 15 1 0 33 27 1 0 23 18 1 0 1 42 1 0 1 43 1 0 1 44 1 0 2 45 1 6 3 46 1 1 4 47 1 6 5 48 1 1 6 49 1 6 10 50 1 0 11 51 1 0 13 52 1 0 14 53 1 0 16 54 1 0 19 55 1 0 21 56 1 0 22 57 1 0 27 58 1 1 28 59 1 6 29 60 1 1 30 61 1 6 31 62 1 1 32 63 1 0 32 64 1 0 32 65 1 0 34 66 1 0 36 67 1 0 36 68 1 0 36 69 1 0 37 70 1 0 38 71 1 0 40 72 1 0 40 73 1 0 40 74 1 0 41 75 1 0 M END

Standard InCHIKey	RTRRNASIAZHUPE-JIGWJBEDSA-N
Standard InCHI	InChI=1S/C29H34O12/c1-13-21(30)26(35-3)24(33)28(38-13)40-16-7-5-15(6-8-16)19-12-37-20-11-17(9-10-18(20)23(19)32)41-29-25(34)27(36-4)22(31)14(2)39-29/h5-14,21-22,24-31,33-34H,1-4H3/t13-,14-,21-,22-,24+,25+,26+,27+,28-,29-/m0/s1
SMILES	C[C@H]1[C@@H]([C@H]([C@H]([C@@H](O1)Oc1ccc(cc1)c1coc2cc(ccc2c1=O)O[C@H]1[C@@H]([C@@H]([C@H]([C@H](C)O1)O)OC)O)O)OC)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	574.21	Volume:	551.749 ? Van der Waals volume.
Dense:	1.041	LogP:	1.038 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.499 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.889 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	30.0
TPSA:	166.51 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	4.0	Rings:	5.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.319	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.593	Fsp³:	0.483
MCE-18:	110.884 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.597	Fluc inhibitor:	0.315 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.903 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.208 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.318	Promiscuous compounds:	0.176

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.603	MDCK Permeability:	-5.145
Pgp-inhibitor:	0.104	Pgp-substrate:	0.945
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):	0.664
20% Bioavailability (F20%):	0.221	30% Bioavailability (F30%):	0.56
50% Bioavailability (F50%):	0.955

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.406
Plasma Protein Binding (PPB):	92.748%	Volume Distribution (VD):	-0.075
Fu:	6.108% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.985
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.06
BSEP inhibitor:	0.626

ADMET: Metabolism

CYP1A2-inhibitor:	0.034	CYP1A2-substrate:	0.741
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.024
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.998
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.981
HLM stability:	0.006 ? 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):

2.299

Half-life (T1/2):

4.462

ADMET: Toxicity

hERG Blockers:	0.127	hERG Blockers (10um):	0.252
Human Hepatotoxicity (H-HT):	0.697	Drug-induced Liver Injury (DILI):	0.999
AMES Toxicity:	0.96	Rat Oral Acute Toxicity:	0.056
Maximum Recommended Daily Dose:	0.02	Skin Sensitization:	0.926
Carcinogencity:	0.129	Eye Corrosion:	0.0
Eye Irritation:	0.057	Respiratory Toxicity:	0.024
Drug-induced Neurotoxicity:	0.016	Ototoxicity:	0.965
Hematotoxicity:	0.393	Drug-induced Nephrotoxicity:	0.966
Genotoxicity:	0.679	RPMI-8226 Immunitoxicity:	0.386
A549 Cytotoxicity:	0.533	Hek293 Cytotoxicity:	0.269
BCF:	0.879 ? 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:	3.582 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.736 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.281 ? 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
NPO40231	Streptomyces sp. RB1	Strain	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[28006913]
NPO40231	Streptomyces sp. RB1	Strain	Streptomycetaceae	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

Activity Type	# Activity
MIC	4

Activity Type	# Activity
Organism	4

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
NPT85	Organism	Filobasidiella neoformans	Cryptococcus neoformans	MIC	>	100.0	ug.mL-1	PMID[28006913]
NPT1173	Organism	Candida albicans SC5314	Candida albicans SC5314	MIC	>	100.0	ug.mL-1	PMID[28006913]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	100.0	ug.mL-1	PMID[28006913]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	>	100.0	ug.mL-1	PMID[28006913]

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 NPC487214 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	16295
0.1-0.2	31215
0.2-0.3	2023
0.3-0.4	249
0.4-0.5	53
0.5-0.6	16
0.6-0.7	4
0.7-0.8	0
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
0.7429	Intermediate Similarity	NPC25547
0.7397	Intermediate Similarity	NPC487213
0.6667	Remote Similarity	NPC487212
0.6447	Remote Similarity	NPC45165
0.6364	Remote Similarity	NPC211014
0.6	Remote Similarity	NPC182428
0.5976	Remote Similarity	NPC43761
0.5797	Remote Similarity	NPC136095
0.5679	Remote Similarity	NPC161749
0.5595	Remote Similarity	NPC229729
0.5432	Remote Similarity	NPC160515
0.5429	Remote Similarity	NPC479067
0.5412	Remote Similarity	NPC601607
0.5405	Remote Similarity	NPC254741
0.5366	Remote Similarity	NPC478528
0.5352	Remote Similarity	NPC181124
0.5301	Remote Similarity	NPC258035
0.5286	Remote Similarity	NPC185607
0.5278	Remote Similarity	NPC471590
0.5244	Remote Similarity	NPC135345
0.5139	Remote Similarity	NPC186507
0.5072	Remote Similarity	NPC120924

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC487214 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3919
0.1-0.2	5126
0.2-0.3	99
0.3-0.4	3
0.4-0.5	1
0.5-0.6	2
0.6-0.7	0
0.7-0.8	0
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
0.5679	Remote Similarity	NPD4381	Clinical (unspecified phase)
0.5429	Remote Similarity	NPD2796	Phase 2

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