NPASS Compound

Natural Product: NPC479401

Natural Product ID	NPC479401
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	HVTIUGNKNOJFBB-RECXWPGBSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
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 55 58 0 0 0 0 0 0 0 0999 V2000 -6.6895 0.5226 -1.3325 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3320 0.1373 -1.5588 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0086 -0.5079 -2.7574 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0008 -0.7660 -3.7086 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6079 -1.4043 -4.8639 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2915 -1.7661 -5.0586 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3121 -1.5048 -4.1060 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6951 -0.8693 -2.9526 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7639 -0.5751 -1.9518 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1296 0.0064 -0.9027 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4629 -0.9543 -2.1885 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1308 -1.5894 -3.3629 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0622 -1.8451 -4.2840 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4135 -0.6855 -1.1894 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1250 -1.6011 -0.2039 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8570 -1.3356 0.7212 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6039 -0.1766 0.7376 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2842 0.7329 -0.2790 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3098 0.4822 -1.2062 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0694 1.4437 -2.1701 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5863 0.1344 1.6305 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0704 -0.5933 2.7024 C 0 0 1 0 0 0 0 0 0 0 0 0 4.5171 -0.9398 2.4225 C 0 0 1 0 0 0 0 0 0 0 0 0 5.3173 0.3174 2.4424 C 0 0 2 0 0 0 0 0 0 0 0 0 4.5435 1.5123 2.9298 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5964 1.2258 4.0350 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5369 2.3383 4.0251 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6475 2.1860 5.0917 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9065 0.0382 3.9215 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4459 2.4856 3.3618 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7888 0.5259 1.1254 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0124 -1.8399 3.3395 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5855 -1.6762 -5.8374 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.3592 -0.3764 -1.3315 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7841 0.9854 -0.3405 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0601 1.1807 -2.1330 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0025 -0.4573 -3.4910 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9795 -2.2697 -5.9694 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0934 -1.8651 -3.4965 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6519 -2.5305 -0.1352 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0680 -2.0789 1.4948 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8663 1.6624 -0.2852 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2164 2.4286 -1.9547 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5282 -1.5559 2.7697 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5256 -1.4454 1.4310 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2301 0.1502 3.0471 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0277 1.9412 2.0298 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0773 1.3020 5.0357 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0043 3.3354 4.1024 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9839 2.2775 3.0444 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7880 1.7978 4.7702 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0201 3.2458 3.8078 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4341 1.2808 1.1034 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0190 -1.4594 4.2470 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3405 -1.0076 -6.0154 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 11 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 17 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 26 29 1 0 25 30 1 0 24 31 1 0 23 32 1 0 5 33 1 0 8 3 1 0 19 14 1 0 29 22 1 0 13 7 1 0 1 34 1 0 1 35 1 0 1 36 1 0 4 37 1 0 6 38 1 0 12 39 1 0 15 40 1 0 16 41 1 0 18 42 1 0 20 43 1 0 22 44 1 1 23 45 1 6 24 46 1 1 25 47 1 6 26 48 1 1 27 49 1 0 27 50 1 0 28 51 1 0 30 52 1 0 31 53 1 0 32 54 1 0 33 55 1 0 M END

Standard InCHIKey	HVTIUGNKNOJFBB-RECXWPGBSA-N
Standard InCHI	InChI=1S/C22H22O11/c1-30-14-4-9(24)5-15-17(14)18(26)12(8-31-15)11-3-2-10(6-13(11)25)32-22-21(29)20(28)19(27)16(7-23)33-22/h2-6,8,16,19-25,27-29H,7H2,1H3/t16-,19-,20+,21-,22-/m1/s1
SMILES	COc1cc(cc2c1c(=O)c(co2)c1ccc(cc1O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	462.12	Volume:	430.443 ? Van der Waals volume.
Dense:	1.074	LogP:	0.556 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.107 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.943 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	24.0
TPSA:	179.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	6.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.302	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.993	Fsp³:	0.318
MCE-18:	86.966 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.54	Fluc inhibitor:	0.278 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.764 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.742 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.096	Promiscuous compounds:	0.334

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.292	MDCK Permeability:	-5.295
Pgp-inhibitor:	0.0	Pgp-substrate:	0.152
PAMPA:	0.971 ? 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):	0.337
20% Bioavailability (F20%):	0.23	30% Bioavailability (F30%):	0.954
50% Bioavailability (F50%):	0.977

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.008	MRP1:	0.172
Plasma Protein Binding (PPB):	78.757%	Volume Distribution (VD):	-0.085
Fu:	19.833% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.227
BSEP inhibitor:	0.002

ADMET: Metabolism

CYP1A2-inhibitor:	0.088	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:	0.002
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.121
HLM stability:	0.002 ? 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):

2.231

Half-life (T1/2):

4.139

ADMET: Toxicity

hERG Blockers:	0.045	hERG Blockers (10um):	0.142
Human Hepatotoxicity (H-HT):	0.717	Drug-induced Liver Injury (DILI):	0.963
AMES Toxicity:	0.916	Rat Oral Acute Toxicity:	0.063
Maximum Recommended Daily Dose:	0.125	Skin Sensitization:	0.975
Carcinogencity:	0.404	Eye Corrosion:	0.0
Eye Irritation:	0.481	Respiratory Toxicity:	0.078
Drug-induced Neurotoxicity:	0.013	Ototoxicity:	0.872
Hematotoxicity:	0.193	Drug-induced Nephrotoxicity:	0.696
Genotoxicity:	0.91	RPMI-8226 Immunitoxicity:	0.145
A549 Cytotoxicity:	0.389	Hek293 Cytotoxicity:	0.424
BCF:	0.415 ? 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:	3.088 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.599 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.697 ? 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
NPO16444	Apios americana	Species	Fabaceae	Eukaryota	Tubers	n.a.	n.a.	PMID[29932657]
NPO16444	Apios americana	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

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
IC50	1

Activity Type	# Activity
Cell line	1

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
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	470.0	nM	PMID[29932657]

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 NPC479401 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	14020
0.1-0.2	31029
0.2-0.3	3633
0.3-0.4	928
0.4-0.5	206
0.5-0.6	32
0.6-0.7	5
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8133	Intermediate Similarity	NPC479402
0.7532	Intermediate Similarity	NPC138540
0.7051	Intermediate Similarity	NPC234739
0.7037	Intermediate Similarity	NPC479406
0.6463	Remote Similarity	NPC100720
0.622	Remote Similarity	NPC258035
0.622	Remote Similarity	NPC156457
0.619	Remote Similarity	NPC80140
0.6145	Remote Similarity	NPC73511
0.5977	Remote Similarity	NPC479407
0.5882	Remote Similarity	NPC599850
0.5811	Remote Similarity	NPC121527
0.5783	Remote Similarity	NPC45165
0.5783	Remote Similarity	NPC135345
0.5765	Remote Similarity	NPC100818
0.5647	Remote Similarity	NPC197896
0.5647	Remote Similarity	NPC105511
0.5647	Remote Similarity	NPC313163
0.5647	Remote Similarity	NPC161749
0.5632	Remote Similarity	NPC481043
0.5568	Remote Similarity	NPC229729
0.5529	Remote Similarity	NPC83283
0.5517	Remote Similarity	NPC222936
0.5517	Remote Similarity	NPC205076
0.5465	Remote Similarity	NPC603782
0.5465	Remote Similarity	NPC609879
0.5341	Remote Similarity	NPC472459
0.5333	Remote Similarity	NPC307518
0.5312	Remote Similarity	NPC479403
0.52	Remote Similarity	NPC7013
0.5172	Remote Similarity	NPC143851
0.5165	Remote Similarity	NPC607201
0.5128	Remote Similarity	NPC279668
0.5128	Remote Similarity	NPC12175
0.5114	Remote Similarity	NPC64305
0.5114	Remote Similarity	NPC95090
0.5114	Remote Similarity	NPC27408
0.5111	Remote Similarity	NPC224462
0.5109	Remote Similarity	NPC48773
0.506	Remote Similarity	NPC78697
0.5057	Remote Similarity	NPC160515

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC479401 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4176
0.1-0.2	4865
0.2-0.3	95
0.3-0.4	10
0.4-0.5	3
0.5-0.6	1
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
0.5647	Remote Similarity	NPD4381	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