NPASS Compound

Natural Product: NPC470158

Natural Product ID	NPC470158
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	OQECEDMGMJXABR-HWHZAUSRSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1796140
PubChem CID	44598262
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids [CHEMONTID:0002051] Agarofurans

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 66 69 0 0 0 0 0 0 0 0999 V2000 1.3414 3.4212 0.9773 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3245 2.3747 1.3418 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2998 1.8494 2.4932 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6257 1.9319 0.4615 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6060 0.9348 0.7938 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9667 1.5639 0.6847 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1093 0.6551 0.4964 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9269 -0.4778 -0.4703 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6169 -1.0990 -0.2195 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4326 -0.1340 -0.2605 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3924 0.6128 -1.5949 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1539 -0.8961 -0.1611 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9733 -0.1662 0.2020 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1092 0.0433 -0.5588 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0853 -0.4877 -1.6719 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2509 0.8266 -0.0949 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2757 0.9478 -0.9288 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4908 1.6730 -0.6680 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6729 2.3172 0.5224 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8393 3.0069 0.7593 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8469 3.0790 -0.1616 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6371 2.4171 -1.3603 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4845 1.7263 -1.6146 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2691 -2.2268 0.5472 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4249 -3.0243 0.0565 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2191 -2.2703 -1.0305 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2739 -3.0744 -1.4311 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4841 -2.8881 1.1712 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7152 -1.5556 1.1201 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5958 -3.8293 1.0192 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7892 -3.2260 2.5012 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2902 -0.0639 -1.8330 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1292 3.4596 1.7349 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7042 3.3021 -0.0508 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7936 4.4014 1.0381 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4885 0.5801 1.8223 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0240 2.3773 -0.0691 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1348 2.1037 1.6667 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4109 0.2427 1.5045 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9781 1.2458 0.1478 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6997 -1.2455 -0.1521 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7931 1.6440 -1.5091 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8131 0.0243 -2.4201 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3164 0.7940 -1.9077 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1020 -1.2385 -1.2166 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2945 1.2904 0.8581 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2043 0.4517 -1.9189 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9383 2.3066 1.2839 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0011 3.5250 1.7002 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7620 3.6103 0.0033 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4467 2.4791 -2.0916 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4077 1.2384 -2.5815 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6653 -2.8092 0.2908 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2257 -2.0710 1.6277 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2316 -4.0547 -0.2082 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6130 -2.0681 -1.9167 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4046 -3.1257 -2.3945 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4914 -3.5307 0.5061 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9293 -4.2364 2.0208 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2084 -4.7503 0.4907 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4641 -3.8634 3.1477 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8930 -3.8578 2.3372 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6035 -2.3222 3.1035 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4248 -0.0167 -1.8781 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0439 -0.8168 -2.6254 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9966 0.9692 -2.1305 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 6 10 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 12 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 25 28 1 0 28 29 1 0 28 30 1 0 28 31 1 0 8 32 1 0 10 5 1 0 23 18 1 0 9 29 1 1 26 9 1 0 1 33 1 0 1 34 1 0 1 35 1 0 5 36 1 1 6 37 1 0 6 38 1 0 7 39 1 0 7 40 1 0 8 41 1 1 11 42 1 0 11 43 1 0 11 44 1 0 12 45 1 6 16 46 1 0 17 47 1 0 19 48 1 0 20 49 1 0 21 50 1 0 22 51 1 0 23 52 1 0 24 53 1 0 24 54 1 0 25 55 1 6 26 56 1 6 27 57 1 0 30 58 1 0 30 59 1 0 30 60 1 0 31 61 1 0 31 62 1 0 31 63 1 0 32 64 1 0 32 65 1 0 32 66 1 0 M END

Standard InCHIKey	OQECEDMGMJXABR-HWHZAUSRSA-N
Standard InCHI	InChI=1S/C26H34O6/c1-16-11-13-20(30-17(2)27)25(5)21(15-19-23(29)26(16,25)32-24(19,3)4)31-22(28)14-12-18-9-7-6-8-10-18/h6-10,12,14,16,19-21,23,29H,11,13,15H2,1-5H3/b14-12+/t16-,19-,20+,21+,23-,25+,26-/m1/s1
SMILES	CC(=O)O[C@H]1CC[C@H]([C@@]23[C@]1(C)[C@@H](OC(=O)/C=C/c1ccccc1)C[C@H]([C@H]3O)C(O2)(C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	442.24	Volume:	460.949 ? Van der Waals volume.
Dense:	0.959	LogP:	3.227 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.151 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.63 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	23.0
TPSA:	82.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.562	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.601	Fsp³:	0.615
MCE-18:	131.19 ? 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:	0.729	Fluc inhibitor:	0.858 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.05 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.152 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.085	Promiscuous compounds:	0.407

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.144	MDCK Permeability:	-4.879
Pgp-inhibitor:	0.995	Pgp-substrate:	0.01
PAMPA:	0.173 ? 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%):	0.716	30% Bioavailability (F30%):	0.838
50% Bioavailability (F50%):	0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.628	MRP1:	0.462
Plasma Protein Binding (PPB):	96.116%	Volume Distribution (VD):	-0.396
Fu:	3.497% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.1
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.137
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.526
CYP2C9-inhibitor:	0.085	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.996
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.154 ? 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):

9.966

Half-life (T1/2):

0.856

ADMET: Toxicity

hERG Blockers:	0.073	hERG Blockers (10um):	0.445
Human Hepatotoxicity (H-HT):	0.638	Drug-induced Liver Injury (DILI):	0.782
AMES Toxicity:	0.738	Rat Oral Acute Toxicity:	0.228
Maximum Recommended Daily Dose:	0.605	Skin Sensitization:	0.996
Carcinogencity:	0.706	Eye Corrosion:	0.024
Eye Irritation:	0.828	Respiratory Toxicity:	0.203
Drug-induced Neurotoxicity:	0.365	Ototoxicity:	0.358
Hematotoxicity:	0.181	Drug-induced Nephrotoxicity:	0.768
Genotoxicity:	0.77	RPMI-8226 Immunitoxicity:	0.064
A549 Cytotoxicity:	0.149	Hek293 Cytotoxicity:	0.505
BCF:	0.723 ? 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:	3.569 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.307 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.714 ? 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
NPO15653	Celastrus vulcanicola	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18616221]
NPO15653	Celastrus vulcanicola	Species	Celastraceae	Eukaryota	stems	Montecristo National Park, province of Santa Ana, El Salvador	2004-JUN	PMID[20873773]
NPO15653	Celastrus vulcanicola	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21419633]
NPO15653	Celastrus vulcanicola	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25695368]
NPO15653	Celastrus vulcanicola	Species	Celastraceae	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
MIC	2

Activity Type	# Activity
Organism	2

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
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	MIC	=	25.0	ug.mL-1	DrugMatrix in vivo data: Pathology
NPT790	Organism	Mycobacterium tuberculosis H37Rv	Mycobacterium tuberculosis H37Rv	MIC	>	25.0	ug.mL-1	Open TG-GATES in vivo data: Biochemistry

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 NPC470158 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	6994
0.1-0.2	36237
0.2-0.3	6173
0.3-0.4	342
0.4-0.5	91
0.5-0.6	12
0.6-0.7	7
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
0.6667	Remote Similarity	NPC100913
0.6622	Remote Similarity	NPC29704
0.6622	Remote Similarity	NPC470157
0.6471	Remote Similarity	NPC84129
0.6447	Remote Similarity	NPC483866
0.6377	Remote Similarity	NPC311175
0.6267	Remote Similarity	NPC476972
0.575	Remote Similarity	NPC174982
0.5679	Remote Similarity	NPC171525
0.5385	Remote Similarity	NPC210591
0.5244	Remote Similarity	NPC70403
0.5244	Remote Similarity	NPC177940
0.5135	Remote Similarity	NPC118080
0.5132	Remote Similarity	NPC475933
0.5125	Remote Similarity	NPC488909
0.5125	Remote Similarity	NPC488905
0.5067	Remote Similarity	NPC37641
0.5067	Remote Similarity	NPC114927
0.5057	Remote Similarity	NPC476973

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470158 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2807
0.1-0.2	6014
0.2-0.3	324
0.3-0.4	5
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