NPASS Compound

Natural Product: NPC601893

Natural Product ID	NPC601893
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	BWUZZVCYDQUXQD-LMFCIFFHSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3911386
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 55 56 0 0 0 0 0 0 0 0999 V2000 -5.3792 2.9174 0.7937 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2068 1.7738 0.8349 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6330 0.5119 0.8254 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2633 0.3713 0.7760 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6186 -0.8464 0.7635 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1489 -0.8500 0.7090 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7398 -1.8152 1.6641 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6103 -1.3205 -0.6149 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1050 -0.5406 -1.7967 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4966 -0.4325 -1.8134 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2531 -1.4208 -0.6009 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8292 -0.6315 -0.5187 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7324 0.7328 -0.3960 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8892 1.4797 -0.3176 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1444 0.8618 -0.3618 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3451 1.7251 -0.2719 C 0 0 1 0 0 0 0 0 0 0 0 0 4.1010 2.6325 0.7684 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5550 0.8885 -0.0166 C 0 0 2 0 0 0 0 0 0 0 0 0 5.3911 0.1503 1.1452 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7470 1.8321 0.1050 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8684 1.0346 0.3315 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2420 -0.5034 -0.4845 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1021 -1.2532 -0.5631 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1487 -2.6528 -0.6893 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4042 -3.2633 -0.7328 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3849 -1.9931 0.8025 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7602 -1.8662 0.8522 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3903 -0.6433 0.8642 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7676 -0.4909 0.9138 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9383 3.8545 0.8383 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6355 2.9268 1.6175 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7823 2.8282 -0.1545 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6839 1.3082 0.7459 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7712 0.1331 0.9436 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1146 -1.6079 2.5600 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0016 -2.4061 -0.7921 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8079 -1.0912 -2.7381 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7027 0.4672 -1.9195 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8511 -0.3227 -2.7319 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2226 1.2772 -0.3527 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8063 2.5686 -0.2198 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4794 2.3418 -1.1906 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6597 2.3933 1.5668 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7827 0.2251 -0.8628 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2195 0.0681 1.6759 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5942 2.5723 0.9070 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8828 2.3838 -0.8411 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5525 1.1780 -0.3558 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2161 -0.9778 -0.5179 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9919 -2.9779 0.1436 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2611 -4.3680 -0.7464 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8874 -2.9724 -1.6974 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8753 -2.9313 0.7923 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3730 -2.7586 0.8832 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3159 -0.5004 0.0468 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 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 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 16 18 1 0 18 19 1 0 18 20 1 0 20 21 1 0 15 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 5 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 28 3 1 0 23 12 1 0 1 30 1 0 1 31 1 0 1 32 1 0 4 33 1 0 6 34 1 1 7 35 1 0 8 36 1 6 9 37 1 0 9 38 1 0 10 39 1 0 13 40 1 0 14 41 1 0 16 42 1 6 17 43 1 0 18 44 1 6 19 45 1 0 20 46 1 0 20 47 1 0 21 48 1 0 22 49 1 0 25 50 1 0 25 51 1 0 25 52 1 0 26 53 1 0 27 54 1 0 29 55 1 0 M END

Standard InCHIKey	BWUZZVCYDQUXQD-LMFCIFFHSA-N
Standard InCHI	InChI=1S/C20H26O9/c1-27-16-7-12(3-5-13(16)23)20(26)18(10-22)29-15-6-4-11(8-17(15)28-2)19(25)14(24)9-21/h3-8,14,18-26H,9-10H2,1-2H3/t14-,18-,19-,20-/m1/s1
SMILES	COc1cc([C@@H](O)[C@@H](CO)Oc2ccc([C@@H](O)[C@H](O)CO)cc2OC)ccc1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	410.16	Volume:	400.657 ? Van der Waals volume.
Dense:	1.024	LogP:	-0.5 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.003 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.22 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	12.0
TPSA:	149.07 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	6.0	Rings:	2.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.324	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.653	Fsp³:	0.4
MCE-18:	32.0 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.625	Fluc inhibitor:	0.327 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.029 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.088 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.316	Promiscuous compounds:	0.446

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.19	MDCK Permeability:	-4.89
Pgp-inhibitor:	0.0	Pgp-substrate:	0.036
PAMPA:	0.988 ? 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):	0.001
20% Bioavailability (F20%):	0.031	30% Bioavailability (F30%):	0.613
50% Bioavailability (F50%):	0.928

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.12
Plasma Protein Binding (PPB):	65.136%	Volume Distribution (VD):	0.17
Fu:	33.082% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.996
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.017
BSEP inhibitor:	0.004

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.003	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.006
CYP2D6-inhibitor:	0.986	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.121
HLM stability:	0.049 ? 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):

4.749

Half-life (T1/2):

2.463

ADMET: Toxicity

hERG Blockers:	0.036	hERG Blockers (10um):	0.332
Human Hepatotoxicity (H-HT):	0.658	Drug-induced Liver Injury (DILI):	0.093
AMES Toxicity:	0.557	Rat Oral Acute Toxicity:	0.03
Maximum Recommended Daily Dose:	0.079	Skin Sensitization:	0.622
Carcinogencity:	0.188	Eye Corrosion:	0.0
Eye Irritation:	0.057	Respiratory Toxicity:	0.015
Drug-induced Neurotoxicity:	0.124	Ototoxicity:	0.985
Hematotoxicity:	0.089	Drug-induced Nephrotoxicity:	0.89
Genotoxicity:	0.136	RPMI-8226 Immunitoxicity:	0.074
A549 Cytotoxicity:	0.266	Hek293 Cytotoxicity:	0.252
BCF:	0.197 ? 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:	2.459 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.915 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.122 ? 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
NPO12173	Zantedeschia aethiopica	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/S0031-9422(98)00092-2]
NPO12173	Zantedeschia aethiopica	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25924520]
NPO12173	Zantedeschia aethiopica	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12173	Zantedeschia aethiopica	Species	Araceae	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
Activity	5
Inhibition	8
IC50	4

Activity Type	# Activity
No target	6
Organism	1
Non-molecular	10

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
NPT28833	No target	No relevant target	n.a.	Activity	=	26.0	umol/L	PMID[27765508]
NPT28833	No target	No relevant target	n.a.	IC50	=	89000.0	nM	PMID[27765508]
NPT28833	No target	No relevant target	n.a.	IC50	=	10700.0	nM	PMID[27765508]
NPT28833	No target	No relevant target	n.a.	Activity	=	18.5	umol/L	PMID[27765508]
NPT28833	No target	No relevant target	n.a.	Activity	=	12.0	umol/L	PMID[27765508]
NPT28833	No target	No relevant target	n.a.	Activity	=	66.3	umol/L	PMID[27765508]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	2.4	%	PMID[27765508]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	52.5	%	PMID[27765508]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	-1.2	%	PMID[27765508]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	94200.0	nM	PMID[27765508]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	100000.0	nM	PMID[27765508]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	-2.9	%	PMID[27765508]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	2.6	%	PMID[27765508]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	30.8	%	PMID[27765508]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	4.4	%	PMID[27765508]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	21.2	%	PMID[27765508]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	Activity	n.a.	n.a.	n.a.	PMID[27765508]

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 NPC601893 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	22364
0.1-0.2	23425
0.2-0.3	3544
0.3-0.4	432
0.4-0.5	51
0.5-0.6	21
0.6-0.7	14
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
0.7407	Intermediate Similarity	NPC9370
0.7407	Intermediate Similarity	NPC287495
0.6897	Remote Similarity	NPC111247
0.6897	Remote Similarity	NPC292056
0.6875	Remote Similarity	NPC35071
0.6875	Remote Similarity	NPC177475
0.6875	Remote Similarity	NPC148615
0.678	Remote Similarity	NPC147821
0.678	Remote Similarity	NPC319625
0.678	Remote Similarity	NPC183181
0.678	Remote Similarity	NPC41706
0.6667	Remote Similarity	NPC476387
0.6667	Remote Similarity	NPC237594
0.6667	Remote Similarity	NPC119060
0.629	Remote Similarity	NPC472969
0.625	Remote Similarity	NPC310854
0.5968	Remote Similarity	NPC481839
0.5918	Remote Similarity	NPC135961
0.5806	Remote Similarity	NPC75695
0.5797	Remote Similarity	NPC114119
0.5797	Remote Similarity	NPC471415
0.5738	Remote Similarity	NPC16208
0.5714	Remote Similarity	NPC267291
0.5676	Remote Similarity	NPC470413
0.5645	Remote Similarity	NPC7903
0.5645	Remote Similarity	NPC160991
0.5556	Remote Similarity	NPC163332
0.549	Remote Similarity	NPC181969
0.5484	Remote Similarity	NPC58607
0.5484	Remote Similarity	NPC191037
0.5484	Remote Similarity	NPC178284
0.5323	Remote Similarity	NPC293701
0.5238	Remote Similarity	NPC114901
0.5238	Remote Similarity	NPC48990
0.5224	Remote Similarity	NPC470098
0.5224	Remote Similarity	NPC473266
0.5185	Remote Similarity	NPC470827

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC601893 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4488
0.1-0.2	4449
0.2-0.3	201
0.3-0.4	12
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