NPASS Compound

Natural Product: NPC290926

Natural Product ID	NPC290926
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ZEJUDJOXRYEYKX-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5319451
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000145] Coumarins and derivatives

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 44 45 0 0 0 0 0 0 0 0999 V2000 4.0274 -1.3998 2.0960 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8588 -0.4556 0.8994 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5457 -0.5104 0.5291 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1712 0.2646 -0.5306 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9138 -0.0845 -1.7942 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2738 1.7403 -0.2854 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6885 -0.0404 -0.7930 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0515 0.3560 0.4600 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4902 0.0786 0.2506 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0134 -1.1872 0.3512 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3842 -1.3407 0.1200 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1948 -0.2736 -0.1976 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6491 1.0024 -0.2951 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4441 2.0911 -0.6130 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8238 3.3176 -0.6888 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4695 3.4377 -0.4556 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9396 4.5909 -0.5371 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7677 2.3727 -0.1589 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2993 1.1768 -0.0712 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1953 -2.2314 0.6679 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5528 -3.5696 0.8106 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4983 -1.3705 -1.0864 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9771 -1.2085 2.6215 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0608 -2.4569 1.7444 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1406 -1.3379 2.7782 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2543 0.5380 1.1026 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4846 -0.9289 0.0883 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5546 0.6033 -2.5904 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0076 0.0101 -1.6549 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7002 -1.1360 -2.1298 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1504 2.0169 0.7744 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2309 2.1622 -0.7102 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4633 2.2468 -0.8473 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3026 0.6065 -1.6083 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3270 -0.2005 1.3453 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1249 1.4462 0.6367 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7797 -2.3450 0.2040 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2419 -0.4066 -0.3718 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5012 1.9594 -0.7893 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4074 4.2157 -0.9369 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5837 -3.7377 1.1400 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4340 -4.0565 -0.1883 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8078 -4.0453 1.5046 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2749 -1.9104 -0.7909 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 4 6 1 0 4 7 1 0 7 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 1 0 14 15 2 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 1 0 10 20 1 0 20 21 1 0 7 22 1 0 19 9 1 0 19 13 2 0 1 23 1 0 1 24 1 0 1 25 1 0 2 26 1 0 2 27 1 0 5 28 1 0 5 29 1 0 5 30 1 0 6 31 1 0 6 32 1 0 6 33 1 0 7 34 1 0 8 35 1 0 8 36 1 0 11 37 1 0 12 38 1 0 14 39 1 0 15 40 1 0 21 41 1 0 21 42 1 0 21 43 1 0 22 44 1 0 M END

Standard InCHIKey	ZEJUDJOXRYEYKX-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C17H22O5/c1-5-21-17(2,3)14(18)10-12-13(20-4)8-6-11-7-9-15(19)22-16(11)12/h6-9,14,18H,5,10H2,1-4H3
SMILES	CCOC(C)(C)C(Cc1c(ccc2ccc(=O)oc12)OC)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	306.15	Volume:	316.244 ? Van der Waals volume.
Dense:	0.968	LogP:	2.752 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.515 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.811 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	12.0
TPSA:	68.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.831	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.228	Fsp³:	0.471
MCE-18:	30.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.154	Fluc inhibitor:	0.01 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.989 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.265 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.154	Promiscuous compounds:	0.231

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.621	MDCK Permeability:	-4.673
Pgp-inhibitor:	0.001	Pgp-substrate:	0.0
PAMPA:	0.726 ? 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):	0.001
20% Bioavailability (F20%):	0.434	30% Bioavailability (F30%):	0.226
50% Bioavailability (F50%):	0.188

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.994
Plasma Protein Binding (PPB):	64.791%	Volume Distribution (VD):	0.012
Fu:	33.974% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.985

ADMET: Metabolism

CYP1A2-inhibitor:	0.025	CYP1A2-substrate:	0.552
CYP2C19-inhibitor:	0.974	CYP2C19-substrate:	0.114
CYP2C9-inhibitor:	0.253	CYP2C9-substrate:	0.016
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.924
CYP3A4-inhibitor:	0.975	CYP3A4-substrate:	0.024
CYP2B6-substrate:	0.019	CYP2C8-inhibitor:	0.695
HLM stability:	0.984 ? 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):

8.436

Half-life (T1/2):

0.659

ADMET: Toxicity

hERG Blockers:	0.119	hERG Blockers (10um):	0.447
Human Hepatotoxicity (H-HT):	0.348	Drug-induced Liver Injury (DILI):	0.367
AMES Toxicity:	0.495	Rat Oral Acute Toxicity:	0.193
Maximum Recommended Daily Dose:	0.621	Skin Sensitization:	0.153
Carcinogencity:	0.642	Eye Corrosion:	0.019
Eye Irritation:	0.825	Respiratory Toxicity:	0.592
Drug-induced Neurotoxicity:	0.202	Ototoxicity:	0.48
Hematotoxicity:	0.11	Drug-induced Nephrotoxicity:	0.205
Genotoxicity:	0.516	RPMI-8226 Immunitoxicity:	0.048
A549 Cytotoxicity:	0.054	Hek293 Cytotoxicity:	0.312
BCF:	0.824 ? 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:	3.511 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.003 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.319 ? 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
NPO10969	Epimedium sagittatum	Species	Berberidaceae	Eukaryota	n.a.	leaf	n.a.	PMID[8699184]
NPO10969	Epimedium sagittatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10969	Epimedium sagittatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10969	Epimedium sagittatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10969	Epimedium sagittatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO10969	Epimedium sagittatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO10969	Epimedium sagittatum	Species	Berberidaceae	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 NPC290926 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	8244
0.1-0.2	38082
0.2-0.3	3175
0.3-0.4	238
0.4-0.5	71
0.5-0.6	30
0.6-0.7	10
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
0.7759	Intermediate Similarity	NPC479311
0.7586	Intermediate Similarity	NPC472525
0.7273	Intermediate Similarity	NPC188380
0.7273	Intermediate Similarity	NPC224543
0.7273	Intermediate Similarity	NPC62366
0.7	Intermediate Similarity	NPC472520
0.6667	Remote Similarity	NPC479310
0.6607	Remote Similarity	NPC80170
0.65	Remote Similarity	NPC479313
0.6379	Remote Similarity	NPC185066
0.6316	Remote Similarity	NPC96286
0.6066	Remote Similarity	NPC168710
0.6061	Remote Similarity	NPC479308
0.6034	Remote Similarity	NPC55147
0.6032	Remote Similarity	NPC26954
0.6032	Remote Similarity	NPC38099
0.5932	Remote Similarity	NPC50896
0.5932	Remote Similarity	NPC326600
0.5692	Remote Similarity	NPC479309
0.5692	Remote Similarity	NPC479312
0.5667	Remote Similarity	NPC610664
0.5588	Remote Similarity	NPC485014
0.5574	Remote Similarity	NPC33986
0.5507	Remote Similarity	NPC485015
0.5469	Remote Similarity	NPC153818
0.5469	Remote Similarity	NPC232246
0.541	Remote Similarity	NPC225106
0.541	Remote Similarity	NPC104796
0.541	Remote Similarity	NPC229916
0.541	Remote Similarity	NPC184861
0.541	Remote Similarity	NPC122259
0.541	Remote Similarity	NPC281014
0.541	Remote Similarity	NPC212124
0.541	Remote Similarity	NPC294456
0.5397	Remote Similarity	NPC31849
0.5397	Remote Similarity	NPC85085
0.5333	Remote Similarity	NPC175159
0.5312	Remote Similarity	NPC605506
0.5238	Remote Similarity	NPC199204
0.5238	Remote Similarity	NPC213173
0.5217	Remote Similarity	NPC484113
0.5205	Remote Similarity	NPC87950
0.5075	Remote Similarity	NPC472424
0.5075	Remote Similarity	NPC281241
0.5072	Remote Similarity	NPC55149
0.5072	Remote Similarity	NPC260265

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC290926 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2117
0.1-0.2	6829
0.2-0.3	200
0.3-0.4	4
0.4-0.5	0
0.5-0.6	0
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
		NPD

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