NPASS Compound

Natural Product: NPC119700

Natural Product ID	NPC119700
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Terpendole E
IUPAC Name	n.a.
Synonyms	Terpendole E
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2347650
PubChem CID	10094631
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001640] Naphthopyrans

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 71 76 0 0 0 0 0 0 0 0999 V2000 -2.7784 2.7230 0.3563 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8251 1.4256 -0.0390 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4206 0.4910 1.0246 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9890 -0.6887 0.2747 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.3449 -0.8516 -0.9694 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0007 -0.6601 -0.7641 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6357 0.8378 -0.7021 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5549 1.4444 -2.0798 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3663 0.8666 0.0588 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1286 2.1777 0.5152 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1546 1.8731 1.6405 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2403 1.2138 0.9211 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7743 -0.1720 0.4678 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7199 0.0519 -0.5978 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2934 -1.2896 -1.0842 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0859 -1.3995 -1.6519 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4019 0.7513 -1.7419 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3637 -1.0206 1.5978 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0652 -0.6895 -0.0692 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6391 -1.5049 -0.9612 N 0 0 0 0 0 0 0 0 0 0 0 0 4.9826 -1.4543 -0.8655 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2572 -0.5588 0.1416 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0751 -0.0806 0.6400 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4862 0.8501 1.6569 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6047 -0.3231 0.4426 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6182 -0.9577 -0.2371 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3367 -1.8539 -1.2451 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0149 -2.0920 -1.5480 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4734 -0.6673 0.1490 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8500 -1.9074 -0.4175 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0984 -0.5995 1.5003 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0080 0.4039 -0.7472 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6882 3.3027 -0.4226 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6352 1.4133 -0.8419 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5865 0.2104 1.7014 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1830 1.0709 1.5595 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7148 -1.5967 0.8607 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7889 -1.0397 0.2825 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6199 1.5509 -2.4453 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1937 2.4759 -1.9512 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0353 0.8652 -2.8291 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5939 0.2904 1.0145 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5709 2.8468 0.9956 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7061 2.7722 -0.2153 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5981 1.3048 2.3827 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4586 2.8304 2.1175 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5379 1.8410 0.0608 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9712 -1.5891 -1.9443 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4464 -2.1023 -0.3428 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1478 -1.1588 -2.7260 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3792 -2.4844 -1.5943 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0998 1.7710 -1.9343 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5287 0.7435 -1.6414 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2591 0.1987 -2.7208 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4630 -0.5248 2.6089 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3413 -1.4246 1.5754 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0263 -1.9323 1.7032 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1837 -2.1402 -1.6768 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3424 0.2998 2.5823 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1292 1.7166 1.8496 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8415 0.3679 1.2204 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6600 -0.7794 -0.0088 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1430 -2.3557 -1.7827 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7640 -2.7919 -2.3361 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5143 -2.5940 0.2432 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7465 -1.4758 1.7378 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3772 -0.4318 2.3244 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7992 0.2841 1.5389 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9732 1.4060 -0.3038 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1054 0.1788 -0.8943 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5723 0.3410 -1.7658 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 6 7 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 14 17 1 6 13 18 1 1 13 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 22 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 4 29 1 0 29 30 1 0 29 31 1 0 29 32 1 0 7 2 1 0 14 9 1 0 23 19 2 0 16 6 1 0 28 21 1 0 24 12 1 0 1 33 1 0 2 34 1 6 3 35 1 0 3 36 1 0 4 37 1 1 6 38 1 1 8 39 1 0 8 40 1 0 8 41 1 0 9 42 1 1 10 43 1 0 10 44 1 0 11 45 1 0 11 46 1 0 12 47 1 6 15 48 1 0 15 49 1 0 16 50 1 0 16 51 1 0 17 52 1 0 17 53 1 0 17 54 1 0 18 55 1 0 18 56 1 0 18 57 1 0 20 58 1 0 24 59 1 0 24 60 1 0 25 61 1 0 26 62 1 0 27 63 1 0 28 64 1 0 30 65 1 0 31 66 1 0 31 67 1 0 31 68 1 0 32 69 1 0 32 70 1 0 32 71 1 0 M END

Standard InCHIKey	SVYIMXYKHRBHSG-KYYKPQATSA-N
Standard InCHI	InChI=1S/C28H39NO3/c1-25(2,31)23-15-21(30)27(4)20-11-10-16-14-18-17-8-6-7-9-19(17)29-24(18)28(16,5)26(20,3)13-12-22(27)32-23/h6-9,16,20-23,29-31H,10-15H2,1-5H3/t16-,20+,21+,22-,23-,26-,27+,28+/m0/s1
SMILES	O[C@@H]1C[C@H](O[C@@H]2[C@]1(C)[C@@H]1CC[C@@H]3[C@]([C@]1(CC2)C)(C)c1[nH]c2c(c1C3)cccc2)C(O)(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	437.29	Volume:	468.327 ? Van der Waals volume.
Dense:	0.934	LogP:	3.317 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.348 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.617 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	29.0
TPSA:	65.48 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	3.0	Rings:	6.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.581	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.74	Fsp³:	0.714
MCE-18:	139.75 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.395	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.562 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.009 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.009	Promiscuous compounds:	0.42

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.203	MDCK Permeability:	-4.789
Pgp-inhibitor:	0.448	Pgp-substrate:	0.065
PAMPA:	0.221 ? 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):	0.0
20% Bioavailability (F20%):	0.04	30% Bioavailability (F30%):	0.039
50% Bioavailability (F50%):	0.893

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.871	MRP1:	0.626
Plasma Protein Binding (PPB):	92.722%	Volume Distribution (VD):	-0.214
Fu:	5.332% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.794
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.055
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.034
CYP2C9-inhibitor:	0.382	CYP2C9-substrate:	0.916
CYP2D6-inhibitor:	0.823	CYP2D6-substrate:	0.321
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	0.615
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.994
HLM stability:	0.073 ? 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):

11.996

Half-life (T1/2):

0.896

ADMET: Toxicity

hERG Blockers:	0.229	hERG Blockers (10um):	0.464
Human Hepatotoxicity (H-HT):	0.663	Drug-induced Liver Injury (DILI):	0.313
AMES Toxicity:	0.662	Rat Oral Acute Toxicity:	0.792
Maximum Recommended Daily Dose:	0.942	Skin Sensitization:	0.94
Carcinogencity:	0.909	Eye Corrosion:	0.0
Eye Irritation:	0.464	Respiratory Toxicity:	0.947
Drug-induced Neurotoxicity:	0.273	Ototoxicity:	0.723
Hematotoxicity:	0.276	Drug-induced Nephrotoxicity:	0.785
Genotoxicity:	0.909	RPMI-8226 Immunitoxicity:	0.093
A549 Cytotoxicity:	0.373	Hek293 Cytotoxicity:	0.54
BCF:	2.01 ? 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:	4.308 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.634 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.142 ? 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
NPO4374	Tolypocladium cylindrosporum	Species	Ophiocordycipitaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26356746]
NPO4374	Tolypocladium cylindrosporum	Species	Ophiocordycipitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	8

Activity Type	# Activity
Cell line	4
Individual protein	3
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT832	Individual protein	Kinesin-like protein 1	Homo sapiens	IC50	=	23000.0	nM	PMID[24673739]
NPT832	Individual protein	Kinesin-like protein 1	Homo sapiens	IC50	=	34700.0	nM	PMID[27865702]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT81	Cell line	A549	Homo sapiens	IC50	=	18820.0	nM	PMID[3236005]
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	=	39220.0	nM	PMID[17571903]
NPT179	Cell line	A2780	Homo sapiens	IC50	=	31100.0	nM	PMID[27107949]
NPT111	Cell line	K562	Homo sapiens	IC50	=	38700.0	nM	PMID[8759172]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	12100.0	nM	PMID[27865702]

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 NPC119700 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	16549
0.1-0.2	32112
0.2-0.3	1036
0.3-0.4	117
0.4-0.5	17
0.5-0.6	16
0.6-0.7	10
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
0.8028	Intermediate Similarity	NPC165201
0.6835	Remote Similarity	NPC609321
0.6625	Remote Similarity	NPC231342
0.641	Remote Similarity	NPC602195
0.6386	Remote Similarity	NPC34271
0.6375	Remote Similarity	NPC6093
0.6322	Remote Similarity	NPC600666
0.625	Remote Similarity	NPC198339
0.619	Remote Similarity	NPC20697
0.6071	Remote Similarity	NPC489082
0.6049	Remote Similarity	NPC97525
0.5977	Remote Similarity	NPC18661
0.5862	Remote Similarity	NPC123019
0.5824	Remote Similarity	NPC36356
0.5806	Remote Similarity	NPC609846
0.5747	Remote Similarity	NPC206967
0.5684	Remote Similarity	NPC601417
0.5618	Remote Similarity	NPC489199
0.551	Remote Similarity	NPC606615
0.55	Remote Similarity	NPC302191
0.5393	Remote Similarity	NPC224641
0.5287	Remote Similarity	NPC487209
0.5181	Remote Similarity	NPC99428
0.5172	Remote Similarity	NPC487208
0.5165	Remote Similarity	NPC487204
0.5165	Remote Similarity	NPC235900
0.5165	Remote Similarity	NPC487201

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC119700 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5230
0.1-0.2	3812
0.2-0.3	105
0.3-0.4	3
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