NPASS Compound

Natural Product: NPC475911

Natural Product ID	NPC475911
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	MYPYOQCSDUEJNS-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11026226
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0003530] Pyranoisoflavonoids

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 57 60 0 0 0 0 0 0 0 0999 V2000 -4.4409 2.3432 -0.6764 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5219 2.9652 0.2935 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2306 2.7418 0.2364 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6683 1.8645 -0.7939 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8490 0.7489 -0.2501 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5496 0.8001 -0.3095 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3431 -0.1944 0.1768 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7449 -1.2982 0.7519 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6171 -1.3853 0.8288 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4121 -0.3625 0.3280 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7684 -0.5284 0.4446 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4212 -1.7819 0.3669 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4265 -2.9157 0.4278 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3469 -2.5481 1.4375 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0289 -4.1209 0.7121 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4220 -1.9256 1.4920 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1920 -1.9271 -0.9428 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8075 -0.1771 0.1342 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5695 -0.5287 1.2290 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8586 -0.5335 1.2550 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5302 -0.1842 0.1789 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9207 -0.2057 0.2574 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6561 0.1491 -0.8350 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0026 0.5190 -1.9863 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6225 0.5407 -2.0648 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8795 0.1857 -0.9719 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5029 0.1898 -0.9959 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8708 0.5221 -2.0305 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9514 0.9108 -3.2169 O 0 0 0 0 0 0 0 0 0 0 0 0 9.0377 0.1189 -0.7293 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0699 3.8547 1.3467 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4644 2.8072 -0.5502 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0806 2.5672 -1.7281 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5495 1.2504 -0.5593 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5496 3.2069 0.9587 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0200 2.3955 -1.5232 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4985 1.3702 -1.3661 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0204 1.6653 -0.7605 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3380 -2.1236 1.1566 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9132 -2.9539 -0.5651 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6943 -3.3831 1.6785 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8831 -2.1261 2.3169 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4635 -4.7194 1.2531 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4769 -1.8452 1.1206 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2212 -1.1821 2.2702 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3642 -2.9541 1.9451 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2865 -1.8961 -0.7834 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9685 -2.8924 -1.4472 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8703 -1.1383 -1.6546 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0439 -0.8267 2.1471 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3744 -0.5062 1.1903 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5954 0.8040 -2.8642 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6290 1.8739 -3.3000 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5329 0.5408 0.0334 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0889 4.2378 1.0796 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2115 3.3186 2.3134 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3612 4.6723 1.5444 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 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 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 13 15 1 0 12 16 1 0 12 17 1 0 7 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 25 29 1 0 23 30 1 0 2 31 1 0 10 5 1 0 14 9 1 0 27 18 1 0 26 21 1 0 1 32 1 0 1 33 1 0 1 34 1 0 3 35 1 0 4 36 1 0 4 37 1 0 6 38 1 0 8 39 1 0 13 40 1 0 14 41 1 0 14 42 1 0 15 43 1 0 16 44 1 0 16 45 1 0 16 46 1 0 17 47 1 0 17 48 1 0 17 49 1 0 19 50 1 0 22 51 1 0 24 52 1 0 29 53 1 0 30 54 1 0 31 55 1 0 31 56 1 0 31 57 1 0 M END

Standard InCHIKey	MYPYOQCSDUEJNS-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C25H26O6/c1-13(2)5-6-14-7-15(8-16-9-21(28)25(3,4)31-24(14)16)18-12-30-20-11-17(26)10-19(27)22(20)23(18)29/h5,7-8,10-12,21,26-28H,6,9H2,1-4H3
SMILES	CC(=CCC1=CC(=CC2=C1OC(C(C2)O)(C)C)C3=COC4=CC(=CC(=C4C3=O)O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	422.17	Volume:	435.743 ? Van der Waals volume.
Dense:	0.969	LogP:	3.568 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.963 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.321 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	24.0
TPSA:	100.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.539	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.632	Fsp³:	0.32
MCE-18:	85.909 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.804	Fluc inhibitor:	0.27 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.936 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.436 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.08	Promiscuous compounds:	0.035

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.073	MDCK Permeability:	-4.736
Pgp-inhibitor:	0.007	Pgp-substrate:	0.79
PAMPA:	0.8 ? 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):	0.048
20% Bioavailability (F20%):	0.995	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.919
Plasma Protein Binding (PPB):	89.757%	Volume Distribution (VD):	0.141
Fu:	10.69% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.321
OATP1B3 inhibitor:	0.931	BCRP inhibitor:	0.998
BSEP inhibitor:	0.243

ADMET: Metabolism

CYP1A2-inhibitor:	0.131	CYP1A2-substrate:	0.998
CYP2C19-inhibitor:	0.092	CYP2C19-substrate:	0.427
CYP2C9-inhibitor:	0.03	CYP2C9-substrate:	0.282
CYP2D6-inhibitor:	0.047	CYP2D6-substrate:	0.923
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.987
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.988 ? 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):

6.207

Half-life (T1/2):

1.041

ADMET: Toxicity

hERG Blockers:	0.175	hERG Blockers (10um):	0.651
Human Hepatotoxicity (H-HT):	0.63	Drug-induced Liver Injury (DILI):	0.627
AMES Toxicity:	0.556	Rat Oral Acute Toxicity:	0.826
Maximum Recommended Daily Dose:	0.964	Skin Sensitization:	0.382
Carcinogencity:	0.677	Eye Corrosion:	0.0
Eye Irritation:	0.278	Respiratory Toxicity:	0.954
Drug-induced Neurotoxicity:	0.274	Ototoxicity:	0.811
Hematotoxicity:	0.09	Drug-induced Nephrotoxicity:	0.267
Genotoxicity:	0.981	RPMI-8226 Immunitoxicity:	0.052
A549 Cytotoxicity:	0.591	Hek293 Cytotoxicity:	0.782
BCF:	1.897 ? 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:	4.649 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.316 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.696 ? 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
NPO29113	Erythrina vogelii	Species	Fabaceae	Eukaryota	root bark	n.a.	n.a.	PMID[11908991]
NPO29113	Erythrina vogelii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29113	Erythrina vogelii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29113	Erythrina vogelii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29113	Erythrina vogelii	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

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 NPC475911 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	18642
0.1-0.2	27352
0.2-0.3	3222
0.3-0.4	501
0.4-0.5	101
0.5-0.6	33
0.6-0.7	6
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
0.6761	Remote Similarity	NPC233918
0.6761	Remote Similarity	NPC268059
0.6667	Remote Similarity	NPC128774
0.625	Remote Similarity	NPC213659
0.625	Remote Similarity	NPC326109
0.6111	Remote Similarity	NPC238279
0.5974	Remote Similarity	NPC52889
0.5867	Remote Similarity	NPC475705
0.5753	Remote Similarity	NPC93552
0.561	Remote Similarity	NPC303174
0.56	Remote Similarity	NPC85131
0.56	Remote Similarity	NPC232947
0.55	Remote Similarity	NPC7989
0.5429	Remote Similarity	NPC78341
0.5385	Remote Similarity	NPC485109
0.5352	Remote Similarity	NPC294409
0.5352	Remote Similarity	NPC490701
0.5316	Remote Similarity	NPC474052
0.525	Remote Similarity	NPC74178
0.525	Remote Similarity	NPC107838
0.5224	Remote Similarity	NPC193792
0.5205	Remote Similarity	NPC309154
0.5205	Remote Similarity	NPC200316
0.519	Remote Similarity	NPC479305
0.5185	Remote Similarity	NPC171821
0.5185	Remote Similarity	NPC469405
0.5147	Remote Similarity	NPC39426
0.5147	Remote Similarity	NPC608554
0.5135	Remote Similarity	NPC194653
0.5135	Remote Similarity	NPC481044
0.5125	Remote Similarity	NPC149875
0.5122	Remote Similarity	NPC474960
0.5068	Remote Similarity	NPC19980
0.5068	Remote Similarity	NPC239363
0.5067	Remote Similarity	NPC254702
0.5062	Remote Similarity	NPC231763
0.5062	Remote Similarity	NPC482075
0.5062	Remote Similarity	NPC303197
0.5056	Remote Similarity	NPC324447

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475911 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3789
0.1-0.2	5307
0.2-0.3	48
0.3-0.4	5
0.4-0.5	0
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
0.5147	Remote Similarity	NPD1510	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