NPASS Compound

Natural Product: NPC326205

Natural Product ID	NPC326205
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	UWEHVAXMSWXKRW-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5321317
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0001909] Protoberberine alkaloids and derivatives

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 50 0 0 0 0 0 0 0 0999 V2000 -6.0814 1.7453 0.3796 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3086 0.5951 0.6518 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9641 0.4864 0.3365 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3364 -0.7027 0.6639 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0000 -0.9106 0.3921 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2792 0.0873 -0.2173 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1662 -0.0186 -0.5612 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7507 -1.2003 0.1847 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2204 -1.2474 0.0401 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9035 -0.0901 -0.2584 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2166 1.2139 -0.4423 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8184 1.1638 -0.1050 N 0 0 0 0 0 0 0 0 0 0 0 0 0.2132 2.3969 -0.4624 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0785 2.3073 -1.1964 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9117 1.2691 -0.5404 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2449 1.4883 -0.2741 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2587 -0.1539 -0.3876 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9661 -1.3509 -0.2268 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2914 -2.5158 0.0723 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9210 -2.4437 0.2015 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3219 -1.1152 -0.4149 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5175 0.3011 -0.3359 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2159 0.7948 -0.6739 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0530 -1.7414 1.2891 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4285 -2.9579 1.6281 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1361 1.9553 -0.6971 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1015 1.5638 0.7810 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6782 2.6412 0.8780 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4711 -1.8232 0.6310 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3103 -0.2232 -1.6420 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4937 -1.1074 1.2659 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3605 -2.1665 -0.1953 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6892 2.0175 0.1658 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2823 1.5244 -1.5128 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9103 3.0735 -1.0338 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0156 2.9641 0.4939 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8683 1.9241 -2.2300 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5560 3.2998 -1.2014 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7553 2.4065 -0.5200 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8124 -3.4702 0.2050 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3502 -3.3265 0.4344 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7920 0.5564 0.6898 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2056 0.6571 -1.1040 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7872 -2.7563 2.5133 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1599 -3.7572 1.8536 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8036 -3.3540 0.7972 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 2 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 10 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 18 21 1 0 21 22 1 0 22 23 1 0 4 24 1 0 24 25 1 0 16 3 1 0 15 6 1 0 12 7 1 0 20 9 1 0 23 17 1 0 1 26 1 0 1 27 1 0 1 28 1 0 5 29 1 0 7 30 1 0 8 31 1 0 8 32 1 0 11 33 1 0 11 34 1 0 13 35 1 0 13 36 1 0 14 37 1 0 14 38 1 0 16 39 1 0 19 40 1 0 20 41 1 0 22 42 1 0 22 43 1 0 25 44 1 0 25 45 1 0 25 46 1 0 M END

Standard InCHIKey	UWEHVAXMSWXKRW-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C20H21NO4/c1-22-18-8-13-5-6-21-10-15-12(3-4-17-20(15)25-11-24-17)7-16(21)14(13)9-19(18)23-2/h3-4,8-9,16H,5-7,10-11H2,1-2H3
SMILES	COC1=C(C=C2C3CC4=C(CN3CCC2=C1)C5=C(C=C4)OCO5)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	339.15	Volume:	342.033 ? Van der Waals volume.
Dense:	0.992	LogP:	1.892 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.155 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.662 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	25.0
TPSA:	40.16 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.841	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.998	Fsp³:	0.4
MCE-18:	85.714 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.229	Fluc inhibitor:	0.031 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.31 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.34 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.248

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.727	MDCK Permeability:	-4.748
Pgp-inhibitor:	0.221	Pgp-substrate:	0.035
PAMPA:	0.006 ? 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%):	0.008	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.697

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.91	MRP1:	0.947
Plasma Protein Binding (PPB):	91.971%	Volume Distribution (VD):	0.377
Fu:	7.96% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.875
OATP1B3 inhibitor:	0.99	BCRP inhibitor:	0.486
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.29
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.006
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.994
CYP3A4-inhibitor:	0.984	CYP3A4-substrate:	0.992
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	0.013
HLM stability:	0.969 ? 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):

7.715

Half-life (T1/2):

2.105

ADMET: Toxicity

hERG Blockers:	0.45	hERG Blockers (10um):	0.633
Human Hepatotoxicity (H-HT):	0.506	Drug-induced Liver Injury (DILI):	0.056
AMES Toxicity:	0.676	Rat Oral Acute Toxicity:	0.567
Maximum Recommended Daily Dose:	0.712	Skin Sensitization:	0.76
Carcinogencity:	0.9	Eye Corrosion:	0.002
Eye Irritation:	0.18	Respiratory Toxicity:	0.923
Drug-induced Neurotoxicity:	0.594	Ototoxicity:	0.646
Hematotoxicity:	0.227	Drug-induced Nephrotoxicity:	0.109
Genotoxicity:	0.369	RPMI-8226 Immunitoxicity:	0.052
A549 Cytotoxicity:	0.121	Hek293 Cytotoxicity:	0.461
BCF:	1.977 ? 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:	4.157 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.714 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.924 ? 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
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.3987/COM-96-7609.]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16038566]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	stem	n.a.	PMID[16964757]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18081254]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[23059629]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18366	Papaver commutatum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18366	Papaver commutatum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18366	Papaver commutatum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO18366	Papaver commutatum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO18366	Papaver commutatum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1315	Sinomenium acutum	Species	Menispermaceae	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	6

Activity Type	# Activity
Cell line	6

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
NPT3140	Cell line	MGC-803	Homo sapiens	IC50	=	94300.0	nM	PMID[35286954]
NPT2511	Cell line	HGC-27	Homo sapiens	IC50	=	81000.0	nM	PMID[35286954]
NPT21769	Cell line	GES1	Homo sapiens	IC50	>	150000.0	nM	PMID[35286954]

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 NPC326205 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	34067
0.1-0.2	14287
0.2-0.3	1259
0.3-0.4	143
0.4-0.5	66
0.5-0.6	10
0.6-0.7	12
0.7-0.8	0
0.8-0.85	4
0.85-0.9	3
0.9-0.95	2
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9245	High Similarity	NPC31311
0.9245	High Similarity	NPC234392
0.8727	High Similarity	NPC216459
0.8727	High Similarity	NPC41178
0.8727	High Similarity	NPC138487
0.8148	Intermediate Similarity	NPC210437
0.8148	Intermediate Similarity	NPC16107
0.8148	Intermediate Similarity	NPC106295
0.8	Intermediate Similarity	NPC51957
0.7742	Intermediate Similarity	NPC232514
0.6825	Remote Similarity	NPC606650
0.6719	Remote Similarity	NPC146288
0.6462	Remote Similarity	NPC276944
0.6462	Remote Similarity	NPC238530
0.629	Remote Similarity	NPC39701
0.629	Remote Similarity	NPC184026
0.625	Remote Similarity	NPC204828
0.625	Remote Similarity	NPC295691
0.625	Remote Similarity	NPC207757
0.625	Remote Similarity	NPC54379
0.625	Remote Similarity	NPC5238
0.614	Remote Similarity	NPC128019
0.5938	Remote Similarity	NPC276588
0.5938	Remote Similarity	NPC127674
0.5938	Remote Similarity	NPC278799
0.5909	Remote Similarity	NPC264850
0.5846	Remote Similarity	NPC27887
0.5821	Remote Similarity	NPC2314
0.5672	Remote Similarity	NPC303581
0.5455	Remote Similarity	NPC469817
0.5303	Remote Similarity	NPC7467
0.5147	Remote Similarity	NPC308267

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC326205 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5087
0.1-0.2	3878
0.2-0.3	165
0.3-0.4	17
0.4-0.5	2
0.5-0.6	0
0.6-0.7	0
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	Drug ID	Developmental Stage
0.8148	Intermediate Similarity	NPD4584	Phase 2

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