NPASS Compound

Natural Product: NPC8939

Natural Product ID	NPC8939
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	SXYIRMFQILZOAM-CNNNLJIRSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	104888
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids [CHEMONTID:0002440] Artemisinins

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 47 50 0 0 0 0 0 0 0 0999 V2000 -3.7083 -0.5958 -0.9629 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1988 -0.6106 -0.9477 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7975 -2.0685 -0.8365 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2763 -2.0277 -0.9976 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2459 -1.4308 0.2952 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7246 -1.5768 0.2719 C 0 0 1 0 0 0 0 0 0 0 0 0 2.1918 -2.7097 -0.6277 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4473 -0.3323 -0.1884 C 0 0 2 0 0 0 0 0 0 0 0 0 3.8016 -0.5017 -0.0218 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5127 -0.3213 -1.1992 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0098 0.7001 0.6157 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7164 1.0356 0.1424 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2621 -0.0651 0.5826 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6379 0.2345 0.1532 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8132 1.6924 -0.3008 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8524 2.5903 0.9438 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5254 2.2859 1.6567 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2014 3.4550 2.5982 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4340 2.2467 0.7026 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7161 1.1816 2.4140 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2261 0.0723 1.9968 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1532 0.3923 -1.0106 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1028 -1.2208 -0.1498 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0072 -1.1236 -1.9160 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7707 -0.2426 -1.9031 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2896 -2.6447 -1.6138 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0332 -2.4304 0.2025 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0267 -1.4381 -1.8809 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0508 -3.0797 -1.0278 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1347 -2.1226 1.1057 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1484 -1.8187 1.2900 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3076 -2.7200 -0.5938 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9139 -2.5526 -1.6818 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8739 -3.6974 -0.2364 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2499 -0.0869 -1.2490 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3196 0.7173 -1.5505 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5914 -0.3930 -0.9948 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2268 -1.0074 -2.0014 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8158 1.0521 -0.9615 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3699 0.1368 1.0121 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9777 2.0379 -0.9029 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7431 1.8536 -0.8359 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7121 2.3624 1.5721 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7984 3.6259 0.5740 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1459 4.3345 2.0132 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6679 3.1169 3.2026 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0617 3.6946 3.2475 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 6 8 1 0 8 9 1 0 9 10 1 0 8 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 1 17 19 1 0 17 20 1 0 20 21 1 0 14 2 1 0 13 5 1 0 19 12 1 0 13 21 1 1 1 22 1 0 1 23 1 0 1 24 1 0 2 25 1 6 3 26 1 0 3 27 1 0 4 28 1 0 4 29 1 0 5 30 1 1 6 31 1 1 7 32 1 0 7 33 1 0 7 34 1 0 8 35 1 6 10 36 1 0 10 37 1 0 10 38 1 0 12 39 1 6 14 40 1 1 15 41 1 0 15 42 1 0 16 43 1 0 16 44 1 0 18 45 1 0 18 46 1 0 18 47 1 0 M END

Standard InCHIKey	SXYIRMFQILZOAM-CNNNLJIRSA-N
Standard InCHI	InChI=1S/C16H26O5/c1-9-5-6-12-10(2)13(17-4)18-14-16(12)11(9)7-8-15(3,19-14)20-21-16/h9-14H,5-8H2,1-4H3/t9-,10-,11+,12+,13-,14-,15-,16-/m1/s1
SMILES	C[C@@H]1CC[C@H]2[C@@H](C)[C@H](OC)O[C@H]3[C@]42[C@H]1CC[C@](C)(O3)OO4

Calculated Properties

Physi-Chem Properties

Molecular Weight:	298.18	Volume:	295.018 ? Van der Waals volume.
Dense:	1.011	LogP:	2.269 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.2 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.071 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	19.0
TPSA:	46.15 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.697	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.734	Fsp³:	1.0
MCE-18:	90.0 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.278	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:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.684	Promiscuous compounds:	0.267

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.947	MDCK Permeability:	-4.816
Pgp-inhibitor:	0.523	Pgp-substrate:	0.049
PAMPA:	0.373 ? 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):	0.003
20% Bioavailability (F20%):	0.057	30% Bioavailability (F30%):	0.027
50% Bioavailability (F50%):	0.199

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.022	MRP1:	0.362
Plasma Protein Binding (PPB):	64.345%	Volume Distribution (VD):	0.797
Fu:	15.187% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.982
OATP1B3 inhibitor:	0.846	BCRP inhibitor:	0.101
BSEP inhibitor:	0.931

ADMET: Metabolism

CYP1A2-inhibitor:	0.994	CYP1A2-substrate:	0.009
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.357	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.988	CYP2D6-substrate:	0.261
CYP3A4-inhibitor:	0.729	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.998	CYP2C8-inhibitor:	0.0
HLM stability:	0.996 ? 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):

13.442

Half-life (T1/2):

1.702

ADMET: Toxicity

hERG Blockers:	0.259	hERG Blockers (10um):	0.594
Human Hepatotoxicity (H-HT):	0.727	Drug-induced Liver Injury (DILI):	0.812
AMES Toxicity:	0.842	Rat Oral Acute Toxicity:	0.699
Maximum Recommended Daily Dose:	0.384	Skin Sensitization:	1.0
Carcinogencity:	0.148	Eye Corrosion:	0.082
Eye Irritation:	0.811	Respiratory Toxicity:	0.205
Drug-induced Neurotoxicity:	0.531	Ototoxicity:	0.588
Hematotoxicity:	0.255	Drug-induced Nephrotoxicity:	0.091
Genotoxicity:	0.302	RPMI-8226 Immunitoxicity:	0.252
A549 Cytotoxicity:	0.092	Hek293 Cytotoxicity:	0.352
BCF:	2.56 ? 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:	3.952 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.787 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.57 ? 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
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[ 21030913]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	leaf	n.a.	DOI[10.1007/s11418-006-0112-9]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	flower	n.a.	DOI[10.1007/s11418-006-0112-9]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	stem	n.a.	DOI[10.1007/s11418-006-0112-9]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[6387056]
NPO10506	Artemisia apiacea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10506	Artemisia apiacea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10506	Artemisia apiacea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO10506	Artemisia apiacea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO10506	Artemisia apiacea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10506	Artemisia apiacea	Species	Asteraceae	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 NPC8939 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	29964
0.1-0.2	19854
0.2-0.3	21
0.3-0.4	1
0.4-0.5	0
0.5-0.6	1
0.6-0.7	15
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC5209
1.0	High Similarity	NPC51956
1.0	High Similarity	NPC29005
0.6552	Remote Similarity	NPC30102
0.6552	Remote Similarity	NPC128816
0.6552	Remote Similarity	NPC67158
0.6552	Remote Similarity	NPC484862
0.6078	Remote Similarity	NPC31046
0.6078	Remote Similarity	NPC209666
0.6078	Remote Similarity	NPC53868
0.6078	Remote Similarity	NPC285480
0.6078	Remote Similarity	NPC30443
0.6078	Remote Similarity	NPC260977
0.6078	Remote Similarity	NPC45256
0.6078	Remote Similarity	NPC486251
0.6078	Remote Similarity	NPC486262
0.6078	Remote Similarity	NPC200167
0.6078	Remote Similarity	NPC80142
0.5179	Remote Similarity	NPC148872

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC8939 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7305
0.1-0.2	1834
0.2-0.3	1
0.3-0.4	0
0.4-0.5	0
0.5-0.6	1
0.6-0.7	6
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD2254	Phase 4
0.8261	Intermediate Similarity	NPD2686	Phase 4
0.8261	Intermediate Similarity	NPD2687	Approved
0.6552	Remote Similarity	NPD3669	Phase 4
0.6552	Remote Similarity	NPD3670	Clinical (unspecified phase)
0.6078	Remote Similarity	NPD1779	Approved
0.6078	Remote Similarity	NPD1780	Phase 4
0.6078	Remote Similarity	NPD1810	Approved
0.6078	Remote Similarity	NPD1811	Phase 4
0.5167	Remote Similarity	NPD3710	Pre-clinical

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