NPASS Compound

Natural Product: NPC60966

Natural Product ID	NPC60966
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	OIQZTOOLPDEEEQ-RECXWPGBSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3325485
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0002105] Glycosyl compounds [CHEMONTID:0004165] Phenolic glycosides

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 55 58 0 0 0 0 0 0 0 0999 V2000 9.7021 -0.7670 0.4932 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9105 -1.1329 -0.6032 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5325 -1.2213 -0.4519 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9354 -0.9550 0.7571 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5692 -1.0395 0.9187 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7384 -1.3985 -0.1379 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3443 -1.6634 -1.3447 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7175 -1.5771 -1.5021 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3653 -1.4773 0.0478 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5475 -0.3515 -0.1674 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1505 0.8322 -0.5682 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3807 1.9396 -0.7840 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8381 3.0526 -1.1477 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0094 1.8069 -0.5835 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1710 2.8749 -0.7801 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1710 2.7897 -0.5964 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6978 1.5515 -0.1895 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8683 0.4825 0.0085 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5047 0.6062 -0.1897 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2604 -0.4563 0.0153 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0321 1.4843 -0.0116 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7510 0.3844 0.3798 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.6412 0.6621 1.5826 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.0794 0.7606 1.1239 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.4574 -0.5978 0.5164 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.2849 -1.0997 -0.2996 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.7258 -1.8546 -1.5338 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4266 -3.0037 -1.2350 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5905 0.0371 -0.7145 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6736 -1.4604 1.5873 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1389 1.7263 0.1313 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5663 -0.3691 2.5149 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7527 4.0799 -1.1843 O 0 0 0 0 0 0 0 0 0 0 0 0 9.4858 -1.3347 1.4052 H 0 0 0 0 0 0 0 0 0 0 0 0 10.7755 -0.9714 0.2169 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6563 0.3363 0.6562 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5678 -0.6700 1.6053 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0915 -0.8307 1.8703 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7149 -1.9480 -2.1925 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1349 -1.8002 -2.4858 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2187 0.8940 -0.7128 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8412 3.6383 -0.7521 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2492 -0.4983 0.3264 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1731 -0.5384 0.5669 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3278 1.5927 2.0953 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7193 1.0019 1.9966 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3509 -0.4279 -0.0869 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6020 -1.7055 0.3210 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3165 -1.2380 -2.2194 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7948 -2.1332 -2.0762 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1988 -2.8702 -0.6635 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1089 -0.9069 2.2964 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0648 1.8983 -0.1408 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6864 -0.7692 2.6040 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4631 4.9081 -0.6820 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 6 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 17 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 26 29 1 0 25 30 1 0 24 31 1 0 23 32 1 0 15 33 1 0 8 3 1 0 20 10 1 0 29 22 1 0 19 14 1 0 1 34 1 0 1 35 1 0 1 36 1 0 4 37 1 0 5 38 1 0 7 39 1 0 8 40 1 0 11 41 1 0 16 42 1 0 18 43 1 0 22 44 1 1 23 45 1 1 24 46 1 1 25 47 1 6 26 48 1 1 27 49 1 0 27 50 1 0 28 51 1 0 30 52 1 0 31 53 1 0 32 54 1 0 33 55 1 0 M END

Standard InCHIKey	OIQZTOOLPDEEEQ-RECXWPGBSA-N
Standard InCHI	InChI=1S/C22H22O11/c1-29-10-2-4-11(5-3-10)30-17-8-14(25)18-13(24)6-12(7-15(18)32-17)31-22-21(28)20(27)19(26)16(9-23)33-22/h2-8,16,19-24,26-28H,9H2,1H3/t16-,19-,20+,21-,22-/m1/s1
SMILES	COc1ccc(cc1)Oc1cc(=O)c2c(cc(cc2o1)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	462.12	Volume:	430.443 ? Van der Waals volume.
Dense:	1.074	LogP:	1.171 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.597 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.216 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	24.0
TPSA:	168.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.345	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.915	Fsp³:	0.318
MCE-18:	83.621 ? 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:	0.637	Fluc inhibitor:	0.127 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.595 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.852 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.113	Promiscuous compounds:	0.288

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.069	MDCK Permeability:	-5.051
Pgp-inhibitor:	0.0	Pgp-substrate:	0.35
PAMPA:	0.987 ? 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):	0.925
20% Bioavailability (F20%):	0.417	30% Bioavailability (F30%):	0.985
50% Bioavailability (F50%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.163
Plasma Protein Binding (PPB):	87.461%	Volume Distribution (VD):	-0.207
Fu:	12.392% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.294
BSEP inhibitor:	0.011

ADMET: Metabolism

CYP1A2-inhibitor:	0.174	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.009	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.876	CYP2D6-substrate:	0.086
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.005
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.028 ? 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):

2.236

Half-life (T1/2):

2.852

ADMET: Toxicity

hERG Blockers:	0.065	hERG Blockers (10um):	0.18
Human Hepatotoxicity (H-HT):	0.681	Drug-induced Liver Injury (DILI):	0.993
AMES Toxicity:	0.948	Rat Oral Acute Toxicity:	0.027
Maximum Recommended Daily Dose:	0.091	Skin Sensitization:	0.973
Carcinogencity:	0.506	Eye Corrosion:	0.0
Eye Irritation:	0.343	Respiratory Toxicity:	0.056
Drug-induced Neurotoxicity:	0.007	Ototoxicity:	0.836
Hematotoxicity:	0.237	Drug-induced Nephrotoxicity:	0.572
Genotoxicity:	0.668	RPMI-8226 Immunitoxicity:	0.092
A549 Cytotoxicity:	0.361	Hek293 Cytotoxicity:	0.503
BCF:	0.378 ? 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:	3.101 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.552 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.719 ? 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
NPO12728	Artemisia rupestris	Species	Asteraceae	Eukaryota	Whole plant	n.a.	n.a.	PMID[25127164]
NPO12728	Artemisia rupestris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25176187]
NPO12728	Artemisia rupestris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26696523]
NPO12728	Artemisia rupestris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12728	Artemisia rupestris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12728	Artemisia rupestris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12728	Artemisia rupestris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12728	Artemisia rupestris	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

Activity Type	# Activity
IC50	1

Activity Type	# Activity
Cell line	1

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
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	21420.0	nM	PMID[22871217]

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 NPC60966 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	22580
0.1-0.2	23727
0.2-0.3	2578
0.3-0.4	710
0.4-0.5	226
0.5-0.6	30
0.6-0.7	4
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
0.6296	Remote Similarity	NPC95090
0.6296	Remote Similarity	NPC27408
0.6104	Remote Similarity	NPC191154
0.6026	Remote Similarity	NPC134819
0.5814	Remote Similarity	NPC22832
0.5814	Remote Similarity	NPC243930
0.5647	Remote Similarity	NPC73511
0.5595	Remote Similarity	NPC261866
0.5595	Remote Similarity	NPC39360
0.5595	Remote Similarity	NPC29763
0.5595	Remote Similarity	NPC210003
0.5568	Remote Similarity	NPC311830
0.5568	Remote Similarity	NPC607707
0.5529	Remote Similarity	NPC189142
0.5529	Remote Similarity	NPC77660
0.5465	Remote Similarity	NPC22195
0.5465	Remote Similarity	NPC84362
0.5465	Remote Similarity	NPC21190
0.5412	Remote Similarity	NPC289667
0.5349	Remote Similarity	NPC197896
0.5349	Remote Similarity	NPC313163
0.5349	Remote Similarity	NPC234739
0.5281	Remote Similarity	NPC486578
0.5281	Remote Similarity	NPC601144
0.5172	Remote Similarity	NPC297987
0.5172	Remote Similarity	NPC277205
0.5172	Remote Similarity	NPC37919
0.5172	Remote Similarity	NPC136042
0.5172	Remote Similarity	NPC323593
0.5172	Remote Similarity	NPC203500
0.5169	Remote Similarity	NPC285197
0.5165	Remote Similarity	NPC267254
0.5114	Remote Similarity	NPC181712
0.5057	Remote Similarity	NPC44558

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC60966 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4807
0.1-0.2	4255
0.2-0.3	77
0.3-0.4	7
0.4-0.5	4
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