NPASS Compound

Natural Product: NPC479869

Natural Product ID	NPC479869
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	JUMDGAKAPKIYPD-FNAHDJPLSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	57400240
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0001775] Amaryllidaceae alkaloids [CHEMONTID:0004120] Lycorine-type amaryllidaceae alkaloids

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 68 72 0 0 0 0 0 0 0 0999 V2000 4.1588 -4.2636 1.5655 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8813 -2.7714 1.3284 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5257 -2.1905 2.6804 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1941 -2.1727 0.8968 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8608 -2.6310 0.3904 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4092 -1.4036 -0.0085 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9520 -0.3873 0.5061 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4061 -1.1739 -0.9297 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9755 0.1212 -1.3086 C 0 0 1 0 0 0 0 0 0 0 0 0 1.1634 0.1954 -2.8087 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5639 1.2254 -3.3821 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4181 1.7681 -4.7620 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2508 3.1443 -4.5351 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0539 2.9456 -3.3754 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.4109 4.0966 -2.6240 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4009 3.8864 -1.1491 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5690 5.0144 -0.3410 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5732 4.9200 1.0378 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4089 3.6931 1.6277 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2438 2.5882 0.8082 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2356 2.6521 -0.5518 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0684 1.5470 -1.4851 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1690 2.1540 -2.5446 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5456 0.2558 -1.0794 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9439 -0.2942 0.1333 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6327 -1.4866 0.3052 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9210 -2.1270 -0.7471 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0091 -1.9955 1.5329 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7072 -3.2138 1.6289 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0200 -3.2020 0.9111 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8344 -4.3016 1.0499 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9753 -3.5515 3.0830 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4519 3.8766 3.0043 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3222 5.2554 3.2990 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7151 5.8405 2.0706 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5179 -4.6818 2.3473 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0641 -4.8290 0.6126 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2213 -4.4024 1.8974 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4788 -2.4217 2.9785 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7482 -1.0983 2.7065 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1980 -2.6925 3.4186 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8173 -2.9205 0.3395 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1127 -1.2514 0.3244 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7698 -1.9510 1.8195 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5348 0.8960 -0.7826 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7352 -0.5230 -3.3783 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3221 1.1491 -5.2862 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3732 1.8733 -5.2910 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8578 3.3967 -5.4275 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5473 3.9032 -4.4103 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7753 4.9387 -2.9364 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4674 4.4018 -2.8749 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7021 6.0051 -0.7785 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1194 1.6595 1.2951 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1020 1.3780 -1.9398 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5510 2.8834 -2.1079 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9196 -0.5007 -1.8526 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0849 -2.4639 0.0952 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8746 -2.9554 1.6071 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2439 -4.2268 0.5455 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1244 -5.3021 1.4339 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8509 -4.3538 -0.0424 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8043 -4.1207 1.4548 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4717 -2.8349 3.7599 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6845 -4.5959 3.3181 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0710 -3.4854 3.3233 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2617 5.5467 3.4678 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9783 5.5659 4.1361 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 2 5 1 0 5 6 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 22 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 1 0 29 30 1 0 29 31 1 0 29 32 1 0 19 33 1 0 33 34 1 0 34 35 1 0 24 9 1 0 23 11 1 0 23 14 1 0 21 16 1 0 35 18 1 0 1 36 1 0 1 37 1 0 1 38 1 0 3 39 1 0 3 40 1 0 3 41 1 0 4 42 1 0 4 43 1 0 4 44 1 0 9 45 1 1 10 46 1 0 12 47 1 0 12 48 1 0 13 49 1 0 13 50 1 0 15 51 1 0 15 52 1 0 17 53 1 0 20 54 1 0 22 55 1 6 23 56 1 1 24 57 1 6 30 58 1 0 30 59 1 0 30 60 1 0 31 61 1 0 31 62 1 0 31 63 1 0 32 64 1 0 32 65 1 0 32 66 1 0 34 67 1 0 34 68 1 0 M END

Standard InCHIKey	JUMDGAKAPKIYPD-FNAHDJPLSA-N
Standard InCHI	InChI=1S/C26H33NO8/c1-25(2,3)34-23(28)32-19-9-14-7-8-27-12-15-10-17-18(31-13-30-17)11-16(15)20(21(14)27)22(19)33-24(29)35-26(4,5)6/h9-11,19-22H,7-8,12-13H2,1-6H3/t19-,20-,21+,22+/m0/s1
SMILES	CC(C)(C)OC(=O)O[C@H]1C=C2CCN3Cc4cc5c(cc4[C@@H]([C@@H]23)[C@@H]1OC(=O)OC(C)(C)C)OCO5

Calculated Properties

Physi-Chem Properties

Molecular Weight:	487.22	Volume:	480.97 ? Van der Waals volume.
Dense:	1.013	LogP:	3.621 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.293 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.149 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	25.0
TPSA:	92.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.436	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.416	Fsp³:	0.615
MCE-18:	111.571 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.634	Fluc inhibitor:	0.091 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.458 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.573 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.003	Promiscuous compounds:	0.169

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.966	MDCK Permeability:	-4.727
Pgp-inhibitor:	0.149	Pgp-substrate:	0.123
PAMPA:	0.012 ? 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%):	0.003	30% Bioavailability (F30%):	0.002
50% Bioavailability (F50%):	0.74

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	1.0	MRP1:	0.983
Plasma Protein Binding (PPB):	86.022%	Volume Distribution (VD):	0.218
Fu:	16.612% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.051
OATP1B3 inhibitor:	0.695	BCRP inhibitor:	0.016
BSEP inhibitor:	0.958

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	0.071	CYP2C19-substrate:	0.979
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.997
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.993	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.027	CYP2C8-inhibitor:	0.075
HLM stability:	0.432 ? 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):

7.367

Half-life (T1/2):

0.632

ADMET: Toxicity

hERG Blockers:	0.215	hERG Blockers (10um):	0.485
Human Hepatotoxicity (H-HT):	0.516	Drug-induced Liver Injury (DILI):	0.644
AMES Toxicity:	0.619	Rat Oral Acute Toxicity:	0.69
Maximum Recommended Daily Dose:	0.715	Skin Sensitization:	0.65
Carcinogencity:	0.835	Eye Corrosion:	0.006
Eye Irritation:	0.333	Respiratory Toxicity:	0.77
Drug-induced Neurotoxicity:	0.731	Ototoxicity:	0.376
Hematotoxicity:	0.416	Drug-induced Nephrotoxicity:	0.714
Genotoxicity:	0.951	RPMI-8226 Immunitoxicity:	0.059
A549 Cytotoxicity:	0.228	Hek293 Cytotoxicity:	0.273
BCF:	1.642 ? 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:	4.227 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.897 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.379 ? 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
NPO40778	Alkaloid lycorine	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[22019045]

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
GI50	8

Activity Type	# Activity
Cell line	6
Non-molecular	2

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
NPT83	Cell line	MCF7	Homo sapiens	GI50	=	5000.0	nM	PMID[22019045]
NPT169	Cell line	B16-F10	Mus musculus	GI50	=	4000.0	nM	PMID[22019045]
NPT1125	Cell line	T98G	Homo sapiens	GI50	=	4000.0	nM	PMID[22019045]
NPT81	Cell line	A549	Homo sapiens	GI50	=	3000.0	nM	PMID[22019045]
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	=	20000.0	nM	PMID[22019045]
NPT306	Cell line	PC-3	Homo sapiens	GI50	=	22000.0	nM	PMID[22019045]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI50	=	9000.0	nM	PMID[22019045]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI50	=	4000.0	nM	PMID[22019045]

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 NPC479869 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	20387
0.1-0.2	28751
0.2-0.3	647
0.3-0.4	40
0.4-0.5	8
0.5-0.6	17
0.6-0.7	5
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
0.7463	Intermediate Similarity	NPC474324
0.7353	Intermediate Similarity	NPC475845
0.7143	Intermediate Similarity	NPC474708
0.6986	Remote Similarity	NPC479863
0.6857	Remote Similarity	NPC479870
0.6533	Remote Similarity	NPC479859
0.6375	Remote Similarity	NPC479862
0.6	Remote Similarity	NPC237044
0.5921	Remote Similarity	NPC474325
0.5823	Remote Similarity	NPC479857
0.5769	Remote Similarity	NPC475981
0.5769	Remote Similarity	NPC474745
0.5769	Remote Similarity	NPC479858
0.5733	Remote Similarity	NPC607721
0.5488	Remote Similarity	NPC230098
0.5488	Remote Similarity	NPC479864
0.5479	Remote Similarity	NPC190332
0.5479	Remote Similarity	NPC181653
0.5432	Remote Similarity	NPC479860
0.5432	Remote Similarity	NPC479867
0.5263	Remote Similarity	NPC479856
0.5238	Remote Similarity	NPC479861
0.5233	Remote Similarity	NPC479866
0.52	Remote Similarity	NPC320104
0.5172	Remote Similarity	NPC479865

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC479869 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4090
0.1-0.2	4991
0.2-0.3	68
0.3-0.4	1
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