NPASS Compound

Natural Product: NPC94866

Natural Product ID	NPC94866
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ODFCWXVQZAQDSO-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	432946
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids

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 52 54 0 0 0 0 0 0 0 0999 V2000 5.2286 -0.6418 -1.4018 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5486 -0.6118 -0.0354 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2908 0.3283 0.8780 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1164 -0.2848 -0.1709 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1426 -1.2713 -0.3386 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8137 -0.9209 -0.4611 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2069 -1.9809 -0.6421 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4070 -1.5312 -1.3838 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9920 -0.2128 -0.9521 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1693 -0.3887 0.0171 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8703 -1.7287 -0.2258 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2389 0.6549 -0.2242 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6809 -0.4079 1.4115 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0292 0.8826 1.7802 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3381 1.5961 0.6947 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0287 0.8199 -0.5489 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9527 1.8962 -1.6588 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3875 0.3627 -0.4268 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3447 1.3576 -0.2605 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6852 1.0236 -0.1358 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6230 2.0615 0.0311 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7976 -0.6457 2.2483 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2790 -0.3231 -1.2643 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2052 -1.6463 -1.8566 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7110 0.0835 -2.0739 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5975 -1.6461 0.3945 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8311 1.1037 0.3201 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0657 -0.2702 1.4369 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6163 0.7207 1.6669 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4836 -2.2919 -0.3656 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3904 -2.4894 0.3243 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2948 -2.7714 -1.2783 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1620 -2.3409 -1.3434 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1139 -1.4829 -2.4771 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5560 0.1359 -1.8792 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1356 -1.8785 -1.2811 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8708 -1.6420 0.3003 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3703 -2.5661 0.2727 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8988 0.6473 0.6591 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8731 1.6249 -0.5280 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8631 0.2811 -1.0866 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0026 -1.2377 1.5762 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3368 0.6457 2.6440 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8287 1.5095 2.2586 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9109 2.5466 0.4741 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3774 2.0065 1.1253 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6122 2.8628 -1.2417 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3330 1.5801 -2.4890 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9956 2.0596 -2.0270 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0945 2.4045 -0.2227 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4841 2.9482 -0.4718 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5006 -0.9308 3.1290 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 2 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 10 12 1 0 10 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 16 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 13 22 1 0 20 4 1 0 18 6 2 0 16 9 1 0 1 23 1 0 1 24 1 0 1 25 1 0 2 26 1 0 3 27 1 0 3 28 1 0 3 29 1 0 5 30 1 0 7 31 1 0 7 32 1 0 8 33 1 0 8 34 1 0 9 35 1 0 11 36 1 0 11 37 1 0 11 38 1 0 12 39 1 0 12 40 1 0 12 41 1 0 13 42 1 0 14 43 1 0 14 44 1 0 15 45 1 0 15 46 1 0 17 47 1 0 17 48 1 0 17 49 1 0 19 50 1 0 21 51 1 0 22 52 1 0 M END

Standard InCHIKey	ODFCWXVQZAQDSO-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C20H30O2/c1-12(2)14-10-13-6-7-17-19(3,4)18(22)8-9-20(17,5)15(13)11-16(14)21/h10-12,17-18,21-22H,6-9H2,1-5H3
SMILES	CC(C)c1cc2CCC3C(C)(C)C(CCC3(C)c2cc1O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	302.22	Volume:	338.478 ? Van der Waals volume.
Dense:	0.893	LogP:	3.709 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.418 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.303 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	16.0
TPSA:	40.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.801	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.583	Fsp³:	0.7
MCE-18:	76.353 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.068	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.084 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.017 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.407	Promiscuous compounds:	0.156

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.662	MDCK Permeability:	-4.74
Pgp-inhibitor:	0.133	Pgp-substrate:	0.43
PAMPA:	0.281 ? 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):	0.022
20% Bioavailability (F20%):	0.955	30% Bioavailability (F30%):	0.976
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.019	MRP1:	0.987
Plasma Protein Binding (PPB):	90.22%	Volume Distribution (VD):	0.244
Fu:	16.212% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.973
OATP1B3 inhibitor:	0.991	BCRP inhibitor:	0.115
BSEP inhibitor:	0.951

ADMET: Metabolism

CYP1A2-inhibitor:	0.99	CYP1A2-substrate:	0.167
CYP2C19-inhibitor:	0.986	CYP2C19-substrate:	0.08
CYP2C9-inhibitor:	0.979	CYP2C9-substrate:	0.011
CYP2D6-inhibitor:	0.521	CYP2D6-substrate:	0.163
CYP3A4-inhibitor:	0.94	CYP3A4-substrate:	0.186
CYP2B6-substrate:	0.995	CYP2C8-inhibitor:	0.935
HLM stability:	0.744 ? 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):

12.405

Half-life (T1/2):

1.24

ADMET: Toxicity

hERG Blockers:	0.181	hERG Blockers (10um):	0.723
Human Hepatotoxicity (H-HT):	0.459	Drug-induced Liver Injury (DILI):	0.114
AMES Toxicity:	0.245	Rat Oral Acute Toxicity:	0.48
Maximum Recommended Daily Dose:	0.79	Skin Sensitization:	0.498
Carcinogencity:	0.371	Eye Corrosion:	0.015
Eye Irritation:	0.839	Respiratory Toxicity:	0.852
Drug-induced Neurotoxicity:	0.347	Ototoxicity:	0.801
Hematotoxicity:	0.174	Drug-induced Nephrotoxicity:	0.32
Genotoxicity:	0.04	RPMI-8226 Immunitoxicity:	0.052
A549 Cytotoxicity:	0.467	Hek293 Cytotoxicity:	0.5
BCF:	2.118 ? 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:	4.462 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.676 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.196 ? 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
NPO28256	Platycladus orientalis	Species	Cupressaceae	Eukaryota	Leaves and branches	Soorkesh Valley, Gollestan, Iran	n.a.	PMID[15104493]
NPO28256	Platycladus orientalis	Species	Cupressaceae	Eukaryota	leaves	Soorkesh Valley, Gollestan, Iran	n.a.	PMID[15104493]
NPO28256	Platycladus orientalis	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28256	Platycladus orientalis	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28256	Platycladus orientalis	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO28256	Platycladus orientalis	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO28256	Platycladus orientalis	Species	Cupressaceae	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 NPC94866 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	17425
0.1-0.2	31175
0.2-0.3	1083
0.3-0.4	113
0.4-0.5	34
0.5-0.6	13
0.6-0.7	10
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC308311
0.8333	Intermediate Similarity	NPC8776
0.7755	Intermediate Similarity	NPC477137
0.7692	Intermediate Similarity	NPC600507
0.7	Intermediate Similarity	NPC324602
0.6538	Remote Similarity	NPC260323
0.6481	Remote Similarity	NPC192948
0.6481	Remote Similarity	NPC147179
0.6481	Remote Similarity	NPC35797
0.6296	Remote Similarity	NPC150601
0.6296	Remote Similarity	NPC601694
0.625	Remote Similarity	NPC36765
0.6226	Remote Similarity	NPC27252
0.6226	Remote Similarity	NPC472979
0.6182	Remote Similarity	NPC11250
0.5893	Remote Similarity	NPC219112
0.5763	Remote Similarity	NPC58560
0.5614	Remote Similarity	NPC172219
0.5614	Remote Similarity	NPC304510
0.5593	Remote Similarity	NPC471187
0.5536	Remote Similarity	NPC604259
0.541	Remote Similarity	NPC481087
0.5357	Remote Similarity	NPC176279
0.5345	Remote Similarity	NPC606176
0.5345	Remote Similarity	NPC606869
0.5323	Remote Similarity	NPC481011
0.5254	Remote Similarity	NPC137750
0.5172	Remote Similarity	NPC38893

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC94866 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5519
0.1-0.2	3585
0.2-0.3	43
0.3-0.4	3
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