NPASS Compound

Natural Product: NPC91189

Natural Product ID	NPC91189
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	RBAKUBXTGCEYKA-HXGSDTCMSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11523922
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0002875] Tigliane and ingenane diterpenoids [CHEMONTID:0002906] Phorbol esters

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 56 59 0 0 0 0 0 0 0 0999 V2000 -4.6993 2.5009 1.1527 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8148 1.5442 0.3894 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5482 1.7528 0.0802 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0665 0.5850 -0.6606 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9212 -0.5161 -0.1018 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0358 -1.7129 -0.9642 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8187 -2.5586 -0.8632 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6374 -2.1559 -0.4289 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1201 -0.8461 0.0725 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3823 -0.9208 -0.1765 C 0 0 2 0 0 0 0 0 0 0 0 0 2.2670 -1.1111 1.0095 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4918 -1.9506 0.7138 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6682 -1.3941 2.3666 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1669 0.2075 0.3856 C 0 0 2 0 0 0 0 0 0 0 0 0 1.1750 1.2566 0.7432 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2965 1.4733 -0.4910 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2533 1.7596 -1.6377 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6296 0.3325 -0.7494 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.3429 -0.0839 -2.0826 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3416 0.6401 -0.3043 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1679 1.6357 0.1106 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9271 2.2474 1.1753 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3887 2.0694 -0.6402 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9600 -3.9463 -1.2832 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9657 -4.7064 -1.2197 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2256 0.2122 -0.1096 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3776 -0.1195 -0.4265 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6616 -0.8338 1.2184 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3195 2.6424 2.1903 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7385 2.1675 1.1071 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6644 3.5197 0.6764 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0550 2.6859 0.3855 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4905 0.7358 -1.7093 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8839 -2.3331 -0.6062 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2638 -1.4323 -2.0019 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0704 -3.0033 -0.4660 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3436 -0.7412 1.1514 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6627 -1.3509 -1.1576 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1036 -2.8960 0.2369 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0798 -2.1772 1.6057 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1125 -1.4733 -0.0970 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0318 -2.2973 2.3432 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0964 -0.5714 2.7888 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5374 -1.5639 3.0648 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6686 2.2086 0.9377 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5607 1.0185 1.6312 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1967 2.4479 -0.3153 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6034 2.1281 -2.4779 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8724 2.6160 -1.3426 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7733 0.8805 -2.0048 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9744 -0.7752 -2.3605 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5601 1.4866 -1.5480 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2426 2.0703 0.0607 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2174 3.1368 -0.9167 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8939 -4.3403 -1.6474 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0704 -0.1505 1.8392 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 11 13 1 0 11 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 16 18 1 0 18 19 1 6 14 20 1 6 20 21 1 0 21 22 2 0 21 23 1 0 7 24 1 0 24 25 2 0 5 26 1 0 26 27 2 0 5 28 1 1 26 2 1 0 18 4 1 0 18 9 1 0 14 10 1 0 1 29 1 0 1 30 1 0 1 31 1 0 3 32 1 0 4 33 1 6 6 34 1 0 6 35 1 0 8 36 1 0 9 37 1 1 10 38 1 6 12 39 1 0 12 40 1 0 12 41 1 0 13 42 1 0 13 43 1 0 13 44 1 0 15 45 1 0 15 46 1 0 16 47 1 1 17 48 1 0 17 49 1 0 17 50 1 0 19 51 1 0 23 52 1 0 23 53 1 0 23 54 1 0 24 55 1 0 28 56 1 0 M END

Standard InCHIKey	RBAKUBXTGCEYKA-HXGSDTCMSA-N
Standard InCHI	InChI=1S/C22H28O6/c1-11-6-16-20(26,18(11)25)9-14(10-23)7-15-17-19(4,5)21(17,28-13(3)24)8-12(2)22(15,16)27/h6-7,10,12,15-17,26-27H,8-9H2,1-5H3/t12-,15+,16-,17-,20-,21+,22-/m1/s1
SMILES	CC1=C[C@@H]2[C@](CC(=C[C@H]3[C@@H]4C(C)(C)[C@@]4(C[C@@H](C)[C@]23O)OC(=O)C)C=O)(C1=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	388.19	Volume:	394.401 ? Van der Waals volume.
Dense:	0.984	LogP:	1.445 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.757 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.619 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	21.0
TPSA:	100.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.552	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.11	Fsp³:	0.682
MCE-18:	81.297 ? 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:	0.118	Fluc inhibitor:	0.007 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.078 ? 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:	0.33	Promiscuous compounds:	0.516

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.038	MDCK Permeability:	-4.647
Pgp-inhibitor:	0.627	Pgp-substrate:	0.571
PAMPA:	0.891 ? 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):	0.024
20% Bioavailability (F20%):	0.367	30% Bioavailability (F30%):	0.763
50% Bioavailability (F50%):	0.976

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.01	MRP1:	0.962
Plasma Protein Binding (PPB):	49.891%	Volume Distribution (VD):	0.011
Fu:	49.287% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.994	BCRP inhibitor:	0.031
BSEP inhibitor:	0.985

ADMET: Metabolism

CYP1A2-inhibitor:	0.014	CYP1A2-substrate:	0.012
CYP2C19-inhibitor:	0.004	CYP2C19-substrate:	0.085
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.021
CYP3A4-inhibitor:	0.01	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.518
HLM stability:	0.549 ? 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):

5.621

Half-life (T1/2):

1.27

ADMET: Toxicity

hERG Blockers:	0.04	hERG Blockers (10um):	0.267
Human Hepatotoxicity (H-HT):	0.56	Drug-induced Liver Injury (DILI):	0.363
AMES Toxicity:	0.658	Rat Oral Acute Toxicity:	0.66
Maximum Recommended Daily Dose:	0.643	Skin Sensitization:	0.964
Carcinogencity:	0.602	Eye Corrosion:	0.28
Eye Irritation:	0.877	Respiratory Toxicity:	0.8
Drug-induced Neurotoxicity:	0.255	Ototoxicity:	0.278
Hematotoxicity:	0.713	Drug-induced Nephrotoxicity:	0.68
Genotoxicity:	0.965	RPMI-8226 Immunitoxicity:	0.109
A549 Cytotoxicity:	0.11	Hek293 Cytotoxicity:	0.254
BCF:	0.581 ? 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:	3.275 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.068 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.54 ? 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
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	roots	n.a.	n.a.	PMID[16792421]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[21534540]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	whole plants	Panshi, Jilin Province, China	2009-JUN	PMID[21534540]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25453801]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26702644]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	Roots	n.a.	n.a.	PMID[28383891]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	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	1

Activity Type	# Activity
Organism	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
NPT602	Organism	Mycobacterium smegmatis	Mycobacterium smegmatis	MIC	>	400.0	ug.mL-1	PMID[28383891]

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 NPC91189 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	16357
0.1-0.2	31791
0.2-0.3	1586
0.3-0.4	50
0.4-0.5	36
0.5-0.6	12
0.6-0.7	21
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8136	Intermediate Similarity	NPC485733
0.7857	Intermediate Similarity	NPC153036
0.7586	Intermediate Similarity	NPC96739
0.75	Intermediate Similarity	NPC485731
0.7	Intermediate Similarity	NPC158523
0.6935	Remote Similarity	NPC174471
0.6774	Remote Similarity	NPC71889
0.6774	Remote Similarity	NPC475937
0.6719	Remote Similarity	NPC474871
0.6719	Remote Similarity	NPC260786
0.6667	Remote Similarity	NPC170212
0.6462	Remote Similarity	NPC485736
0.6462	Remote Similarity	NPC277477
0.6462	Remote Similarity	NPC479003
0.6462	Remote Similarity	NPC485735
0.6308	Remote Similarity	NPC478681
0.6286	Remote Similarity	NPC183540
0.6269	Remote Similarity	NPC482454
0.6197	Remote Similarity	NPC479000
0.6176	Remote Similarity	NPC17138
0.6176	Remote Similarity	NPC101825
0.6176	Remote Similarity	NPC215643
0.6176	Remote Similarity	NPC265499
0.6087	Remote Similarity	NPC221511
0.6027	Remote Similarity	NPC222307
0.6	Remote Similarity	NPC485732
0.5946	Remote Similarity	NPC159692
0.5833	Remote Similarity	NPC151216
0.5833	Remote Similarity	NPC89227
0.5811	Remote Similarity	NPC602538
0.5526	Remote Similarity	NPC472760
0.5342	Remote Similarity	NPC475391
0.5342	Remote Similarity	NPC477091
0.5205	Remote Similarity	NPC474872
0.52	Remote Similarity	NPC474937
0.5135	Remote Similarity	NPC482317
0.5128	Remote Similarity	NPC153651
0.5075	Remote Similarity	NPC156252

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC91189 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6590
0.1-0.2	2538
0.2-0.3	22
0.3-0.4	0
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