NPASS Compound

Natural Product: NPC249004

Natural Product ID	NPC249004
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	SRELFLQJDOTNLJ-HNNXBMFYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	164601
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0000262] Fatty acids and conjugates [CHEMONTID:0002949] Long-chain fatty acids

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 46 46 0 0 0 0 0 0 0 0999 V2000 1.4957 -0.1552 -1.7548 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7700 0.8616 -0.6932 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1926 1.3506 -0.8209 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1978 0.2406 -0.6720 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0321 -0.4100 0.6683 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2402 0.5731 1.7787 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0864 -0.0820 3.1210 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2405 0.6510 4.1245 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7885 -1.4326 3.2349 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0958 -0.6617 -1.6604 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9125 0.4172 -1.8277 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3373 -0.0891 -1.7509 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5845 -0.7245 -0.4260 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9978 -1.2437 -0.2915 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1863 -1.8660 1.0477 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7693 -1.0160 1.8757 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0291 0.2635 1.1710 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0301 -0.1421 -0.2815 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2213 -1.0096 -1.6185 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6781 0.2133 -2.7734 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0831 1.7385 -0.7546 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6266 0.4270 0.3184 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3267 1.8035 -1.8545 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3497 2.1726 -0.1117 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1455 -0.4829 -1.5056 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2511 0.6696 -0.6914 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0473 -0.9397 0.7560 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8205 -1.2131 0.7162 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2153 1.0457 1.6737 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4499 1.3747 1.7168 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1120 -1.9349 4.0733 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0696 -1.4192 -2.4570 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0039 -1.1502 -0.6520 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7745 0.9007 -2.8144 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8197 1.2297 -1.0673 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9925 0.7955 -1.8866 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4761 -0.8434 -2.5541 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3281 -0.0662 0.4122 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9302 -1.6420 -0.3412 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2443 -1.9831 -1.0732 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8881 -2.8774 1.3133 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0305 -1.1974 2.9171 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0185 0.6503 1.4992 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2237 0.9983 1.3967 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8075 0.6831 -0.9627 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0205 -0.6004 -0.5176 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 1 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 2 0 16 17 1 0 17 18 1 0 18 14 1 0 1 19 1 0 1 20 1 0 2 21 1 0 2 22 1 0 3 23 1 0 3 24 1 0 4 25 1 0 4 26 1 0 5 27 1 0 5 28 1 0 6 29 1 0 6 30 1 0 9 31 1 0 10 32 1 0 10 33 1 0 11 34 1 0 11 35 1 0 12 36 1 0 12 37 1 0 13 38 1 0 13 39 1 0 14 40 1 6 15 41 1 0 16 42 1 0 17 43 1 0 17 44 1 0 18 45 1 0 18 46 1 0 M END

Standard InCHIKey	SRELFLQJDOTNLJ-HNNXBMFYSA-N
Standard InCHI	InChI=1S/C16H28O2/c17-16(18)14-8-6-4-2-1-3-5-7-11-15-12-9-10-13-15/h9,12,15H,1-8,10-11,13-14H2,(H,17,18)/t15-/m0/s1
SMILES	C(CCCCCC(=O)O)CCCC[C@H]1C=CCC1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	252.21	Volume:	289.043 ? Van der Waals volume.
Dense:	0.873	LogP:	4.817 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.909 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.209 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	6.0
TPSA:	37.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	1.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.418	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.711	Fsp³:	0.812
MCE-18:	11.034 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.031	Fluc inhibitor:	0.144 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.004 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.021 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.994	Promiscuous compounds:	0.865

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.077	MDCK Permeability:	-4.739
Pgp-inhibitor:	0.0	Pgp-substrate:	0.022
PAMPA:	0.378 ? 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):	0.19
20% Bioavailability (F20%):	0.349	30% Bioavailability (F30%):	0.798
50% Bioavailability (F50%):	0.33

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.017	MRP1:	0.965
Plasma Protein Binding (PPB):	97.434%	Volume Distribution (VD):	-0.15
Fu:	2.116% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.484
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.095
BSEP inhibitor:	0.237

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.035
CYP2C19-inhibitor:	0.099	CYP2C19-substrate:	0.276
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.047
CYP2D6-inhibitor:	0.091	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.825
CYP2B6-substrate:	0.998	CYP2C8-inhibitor:	0.926
HLM stability:	0.009 ? 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):

3.496

Half-life (T1/2):

0.72

ADMET: Toxicity

hERG Blockers:	0.018	hERG Blockers (10um):	0.065
Human Hepatotoxicity (H-HT):	0.131	Drug-induced Liver Injury (DILI):	0.157
AMES Toxicity:	0.064	Rat Oral Acute Toxicity:	0.094
Maximum Recommended Daily Dose:	0.093	Skin Sensitization:	0.896
Carcinogencity:	0.361	Eye Corrosion:	0.999
Eye Irritation:	1.0	Respiratory Toxicity:	0.635
Drug-induced Neurotoxicity:	0.014	Ototoxicity:	0.184
Hematotoxicity:	0.172	Drug-induced Nephrotoxicity:	0.438
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.019
A549 Cytotoxicity:	0.018	Hek293 Cytotoxicity:	0.019
BCF:	1.071 ? 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:	3.815 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.358 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.246 ? 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
NPO24820	Taxus cuspidata	Species	Taxaceae	Eukaryota	n.a.	Japan	n.a.	PMID[14987066]
NPO24820	Taxus cuspidata	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15844936]
NPO24820	Taxus cuspidata	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15974623]
NPO24820	Taxus cuspidata	Species	Taxaceae	Eukaryota	n.a.	Japan	n.a.	PMID[15974623]
NPO24820	Taxus cuspidata	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24820	Taxus cuspidata	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24820	Taxus cuspidata	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24820	Taxus cuspidata	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO24820	Taxus cuspidata	Species	Taxaceae	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 NPC249004 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	33911
0.1-0.2	14722
0.2-0.3	982
0.3-0.4	117
0.4-0.5	69
0.5-0.6	47
0.6-0.7	3
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC174560
1.0	High Similarity	NPC125312
0.6286	Remote Similarity	NPC168211
0.625	Remote Similarity	NPC55023
0.625	Remote Similarity	NPC21844
0.5882	Remote Similarity	NPC314679
0.5882	Remote Similarity	NPC281245
0.5862	Remote Similarity	NPC214610
0.5862	Remote Similarity	NPC118968
0.5862	Remote Similarity	NPC183424
0.5862	Remote Similarity	NPC294085
0.5758	Remote Similarity	NPC180534
0.5758	Remote Similarity	NPC611531
0.5714	Remote Similarity	NPC424
0.5714	Remote Similarity	NPC36061
0.5714	Remote Similarity	NPC69510
0.5714	Remote Similarity	NPC77272
0.5714	Remote Similarity	NPC290563
0.5714	Remote Similarity	NPC139029
0.5714	Remote Similarity	NPC281972
0.5714	Remote Similarity	NPC261831
0.5714	Remote Similarity	NPC87564
0.5556	Remote Similarity	NPC95145
0.5556	Remote Similarity	NPC325642
0.5556	Remote Similarity	NPC65174
0.5517	Remote Similarity	NPC268826
0.5429	Remote Similarity	NPC34416
0.5312	Remote Similarity	NPC171736
0.5312	Remote Similarity	NPC301585
0.5312	Remote Similarity	NPC261080
0.5312	Remote Similarity	NPC132565
0.5312	Remote Similarity	NPC209970
0.5312	Remote Similarity	NPC216630
0.5312	Remote Similarity	NPC201844
0.5312	Remote Similarity	NPC301696
0.5312	Remote Similarity	NPC196924
0.5312	Remote Similarity	NPC307783
0.5312	Remote Similarity	NPC154186
0.5312	Remote Similarity	NPC149184
0.5312	Remote Similarity	NPC279026
0.5312	Remote Similarity	NPC113928
0.5312	Remote Similarity	NPC14227
0.5278	Remote Similarity	NPC92114
0.5263	Remote Similarity	NPC52955
0.5263	Remote Similarity	NPC88966
0.5263	Remote Similarity	NPC25417
0.5263	Remote Similarity	NPC1813
0.5263	Remote Similarity	NPC154245
0.5263	Remote Similarity	NPC85813
0.5263	Remote Similarity	NPC223697
0.5263	Remote Similarity	NPC6095
0.5152	Remote Similarity	NPC604140

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC249004 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6459
0.1-0.2	2444
0.2-0.3	201
0.3-0.4	28
0.4-0.5	9
0.5-0.6	9
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
0.5862	Remote Similarity	NPD9655	Phase 4
0.5758	Remote Similarity	NPD622	Pre-clinical
0.5714	Remote Similarity	NPD3195	Phase 2
0.5714	Remote Similarity	NPD3196	Approved
0.5312	Remote Similarity	NPD2270	Pre-clinical
0.5312	Remote Similarity	NPD633	Phase 3
0.5312	Remote Similarity	NPD9448	Phase 2
0.5263	Remote Similarity	NPD3172	Approved
0.5263	Remote Similarity	NPD4266	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