NPASS Compound

Natural Product: NPC605051

Natural Product ID	NPC605051
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	HDONJQIYHGHIJV-VCPQXCNPSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL538661
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 46 48 0 0 0 0 0 0 0 0999 V2000 7.9959 -1.6024 -0.4438 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7311 -1.1383 -0.9347 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6593 -0.9891 -0.0781 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7665 -1.2546 1.1425 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3387 -0.5132 -0.5455 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3287 -0.3741 0.2696 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0129 0.0869 -0.1270 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7361 0.4185 -1.4339 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4516 0.8572 -1.7623 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2304 1.1773 -3.0937 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5001 0.9452 -0.7694 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2426 0.6187 0.5412 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0371 0.1834 0.8582 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4808 0.8397 1.3020 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3961 2.2145 1.9073 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4442 2.3383 3.1505 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2675 3.3442 1.1445 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1902 4.6368 1.7645 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5465 0.8798 0.2650 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1760 -0.4223 -0.0170 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4820 -1.4258 -0.6464 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0573 -2.6607 -0.9220 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3715 -2.8883 -0.5509 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9220 -4.1314 -0.8382 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0880 -1.8950 0.0825 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3989 -2.1722 0.4333 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4806 -0.6619 0.3461 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8236 1.3521 -0.8764 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2001 -2.6214 -0.8424 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9442 -1.7201 0.6633 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8056 -0.8983 -0.6761 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2699 -0.2938 -1.5841 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5249 -0.6314 1.3117 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4973 0.3408 -2.1898 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3344 2.1565 -3.3448 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2306 -0.0708 1.8883 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6485 0.0989 2.1004 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2848 5.1546 1.4427 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0696 5.2258 1.4403 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2452 4.5474 2.8662 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3092 1.6744 0.4513 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4556 -1.3064 -0.9584 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5072 -3.4489 -1.4181 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9232 -4.2807 -0.9072 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7167 -1.7877 1.3320 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0675 0.0979 0.8441 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 3 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 9 11 2 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 15 16 2 0 15 17 1 0 17 18 1 0 14 19 1 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 23 25 1 0 25 26 1 0 25 27 2 0 19 28 1 0 13 7 1 0 27 20 1 0 28 11 1 0 1 29 1 0 1 30 1 0 1 31 1 0 5 32 1 0 6 33 1 0 8 34 1 0 10 35 1 0 13 36 1 0 14 37 1 1 18 38 1 0 18 39 1 0 18 40 1 0 19 41 1 1 21 42 1 0 22 43 1 0 24 44 1 0 26 45 1 0 27 46 1 0 M END

Standard InCHIKey	HDONJQIYHGHIJV-VCPQXCNPSA-N
Standard InCHI	InChI=1S/C20H18O8/c1-26-16(24)6-3-10-7-12-17(20(25)27-2)18(28-19(12)15(23)8-10)11-4-5-13(21)14(22)9-11/h3-9,17-18,21-23H,1-2H3/b6-3+/t17-,18+/m1/s1
SMILES	COC(=O)/C=C/c1cc(O)c2c(c1)[C@@H](C(=O)OC)[C@H](c1ccc(O)c(O)c1)O2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	386.1	Volume:	375.4 ? Van der Waals volume.
Dense:	1.029	LogP:	2.477 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.437 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.272 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	19.0
TPSA:	122.52 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.416	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.509	Fsp³:	0.2
MCE-18:	63.333 ? 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:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.956	Fluc inhibitor:	0.997 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.212 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.714 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.521	Promiscuous compounds:	0.376

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.636	MDCK Permeability:	-4.936
Pgp-inhibitor:	0.016	Pgp-substrate:	0.03
PAMPA:	0.608 ? 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):	0.084
20% Bioavailability (F20%):	0.988	30% Bioavailability (F30%):	0.993
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.006	MRP1:	0.915
Plasma Protein Binding (PPB):	80.237%	Volume Distribution (VD):	-0.416
Fu:	19.348% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.98
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.236
BSEP inhibitor:	0.253

ADMET: Metabolism

CYP1A2-inhibitor:	0.237	CYP1A2-substrate:	0.977
CYP2C19-inhibitor:	0.112	CYP2C19-substrate:	0.819
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.007
CYP2D6-inhibitor:	0.003	CYP2D6-substrate:	0.91
CYP3A4-inhibitor:	0.174	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.056 ? 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):

12.513

Half-life (T1/2):

1.555

ADMET: Toxicity

hERG Blockers:	0.094	hERG Blockers (10um):	0.6
Human Hepatotoxicity (H-HT):	0.801	Drug-induced Liver Injury (DILI):	0.789
AMES Toxicity:	0.593	Rat Oral Acute Toxicity:	0.356
Maximum Recommended Daily Dose:	0.872	Skin Sensitization:	0.994
Carcinogencity:	0.231	Eye Corrosion:	0.017
Eye Irritation:	0.916	Respiratory Toxicity:	0.305
Drug-induced Neurotoxicity:	0.171	Ototoxicity:	0.63
Hematotoxicity:	0.054	Drug-induced Nephrotoxicity:	0.364
Genotoxicity:	0.928	RPMI-8226 Immunitoxicity:	0.033
A549 Cytotoxicity:	0.674	Hek293 Cytotoxicity:	0.373
BCF:	0.923 ? 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:	3.68 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.175 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.748 ? 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
NPO12128	Ipomoea purpurea	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12128	Ipomoea purpurea	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12128	Ipomoea purpurea	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO12128	Ipomoea purpurea	Species	Convolvulaceae	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	2
Inhibition	3
GI50	13
Activity	2

Activity Type	# Activity
Cell line	14
Individual protein	4
Non-molecular	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT781	Individual protein	Tubulin alpha chain	Sus scrofa	Inhibition	=	53.0	%	PMID[10639289]
NPT781	Individual protein	Tubulin alpha chain	Sus scrofa	Inhibition	=	14.0	%	PMID[10639289]
NPT956	Individual protein	Prostaglandin E synthase	Homo sapiens	IC50	=	8500.0	nM	PMID[26777299]
NPT956	Individual protein	Prostaglandin E synthase	Homo sapiens	Inhibition	n.a.	n.a.	%	PMID[26777299]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT402	Cell line	Hs-578T	Homo sapiens	GI50	=	45.0	nM	PMID[10639289]
NPT367	Cell line	MDA-N	Homo sapiens	GI50	>	10.0	nM	PMID[10639289]
NPT82	Cell line	MDA-MB-231	Homo sapiens	GI50	=	50.0	nM	PMID[10639289]
NPT457	Cell line	BT-549	Homo sapiens	GI50	>	10.0	nM	PMID[10639289]
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	=	33.0	nM	PMID[10639289]
NPT83	Cell line	MCF7	Homo sapiens	GI50	=	29.0	nM	PMID[10639289]
NPT83	Cell line	MCF7	Homo sapiens	GI50	=	54.0	nM	PMID[10639289]
NPT4461	Cell line	Panel (Carcinoma cell lines)	Homo sapiens	GI50	=	300.0	nM	PMID[10639289]
NPT389	Cell line	RPMI-8226	Homo sapiens	GI50	=	55.0	nM	PMID[10639289]
NPT4461	Cell line	Panel (Carcinoma cell lines)	Homo sapiens	GI50	=	288.4	nM	PMID[10639289]
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	=	81.0	nM	PMID[10639289]
NPT116	Cell line	HL-60	Homo sapiens	IC50	=	200.0	nM	PMID[10639289]
NPT385	Cell line	SR	Homo sapiens	GI50	=	69.0	nM	PMID[10639289]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	n.a.	n.a.	n.a.	PMID[12027748]
NPT29262	Cell line	MDA-MB-4	n.a.	GI50	>	10.0	nM	PMID[10639289]

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 NPC605051 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	20992
0.1-0.2	24486
0.2-0.3	3934
0.3-0.4	409
0.4-0.5	33
0.5-0.6	1
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	Natural Product ID
0.7966	Intermediate Similarity	NPC606425
0.5556	Remote Similarity	NPC134047

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC605051 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4596
0.1-0.2	4468
0.2-0.3	80
0.3-0.4	6
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