NPASS Compound

Structure

CID144863 OpenBabel06191715502D 28 32 0 0 1 0 0 0 0 0999 V2000 -0.8660 5.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 1.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0000 4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 2.5000 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 -0.8660 4.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 26 1 0 0 0 0 2 27 1 0 0 0 0 3 28 1 0 0 0 0 4 5 1 0 0 0 0 4 6 1 0 0 0 0 5 9 1 0 0 0 0 6 15 1 0 0 0 0 7 8 2 0 0 0 0 7 16 1 0 0 0 0 8 17 1 0 0 0 0 9 25 1 0 0 0 0 10 15 1 0 0 0 0 10 18 1 0 0 0 0 11 16 2 0 0 0 0 11 19 1 0 0 0 0 12 20 2 0 0 0 0 12 23 1 0 0 0 0 13 21 2 0 0 0 0 13 24 1 0 0 0 0 14 22 1 0 0 0 0 14 25 1 0 0 0 0 15 25 1 6 0 0 0 16 26 1 0 0 0 0 17 19 2 0 0 0 0 17 22 1 0 0 0 0 18 20 1 0 0 0 0 18 22 2 0 0 0 0 19 21 1 0 0 0 0 20 21 1 0 0 0 0 23 24 2 0 0 0 0 23 27 1 0 0 0 0 24 28 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	377.2
Volume:	399.79
LogP:	5.346
LogD:	3.843
LogS:	-6.297
# Rotatable Bonds:	3
TPSA:	30.93
# H-Bond Aceptor:	4
# H-Bond Donor:	0
# Rings:	5
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.606
Synthetic Accessibility Score:	2.873
Fsp3:	0.417
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.123
MDCK Permeability:	2.471024708938785e-05
Pgp-inhibitor:	0.988
Pgp-substrate:	0.977
Human Intestinal Absorption (HIA):	0.002
20% Bioavailability (F20%):	0.305
30% Bioavailability (F30%):	0.312

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.919
Plasma Protein Binding (PPB):	82.66683197021484%
Volume Distribution (VD):	1.748
Pgp-substrate:	3.9023373126983643%

ADMET: Metabolism

CYP1A2-inhibitor:	0.539
CYP1A2-substrate:	0.977
CYP2C19-inhibitor:	0.209
CYP2C19-substrate:	0.927
CYP2C9-inhibitor:	0.015
CYP2C9-substrate:	0.789
CYP2D6-inhibitor:	0.976
CYP2D6-substrate:	0.941
CYP3A4-inhibitor:	0.077
CYP3A4-substrate:	0.828

ADMET: Excretion

Clearance (CL):	9.31
Half-life (T1/2):	0.149

ADMET: Toxicity

hERG Blockers:	0.571
Human Hepatotoxicity (H-HT):	0.617
Drug-inuced Liver Injury (DILI):	0.956
AMES Toxicity:	0.855
Rat Oral Acute Toxicity:	0.663
Maximum Recommended Daily Dose:	0.903
Skin Sensitization:	0.953
Carcinogencity:	0.232
Eye Corrosion:	0.003
Eye Irritation:	0.02
Respiratory Toxicity:	0.936

Download Data

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General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC144863

Natural Product ID:	NPC144863
*Common Name:**	Cryptopleurine
IUPAC Name:	(14aR)-2,3,6-trimethoxy-11,12,13,14,14a,15-hexahydro-9H-phenanthro[9,10-b]quinolizine
Synonyms:	(-)-Cryptopleurine; Cryptopleurine; R-Cryptopleurine
Standard InCHIKey:	RSHYSOGXGSUUIJ-OAHLLOKOSA-N
Standard InCHI:	InChI=1S/C24H27NO3/c1-26-16-7-8-17-19(11-16)21-13-24(28-3)23(27-2)12-20(21)18-10-15-6-4-5-9-25(15)14-22(17)18/h7-8,11-13,15H,4-6,9-10,14H2,1-3H3/p+1/t15-/m1/s1
SMILES:	COc1ccc2c(c1)c1cc(c(cc1c1C[C@H]3CCCC[NH+]3Cc21)OC)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL198075
PubChem CID:	92765
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000025] Phenanthrenes and derivatives [CHEMONTID:0001907] Phenanthroquinolizidines

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

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Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO9055	Aspergillus novofumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27626956]
NPO24232	Boehmeria pannosa	Species	Urticaceae	Eukaryota	roots	n.a.	n.a.	PMID[16872154]
NPO13539	Thuja occidentalis	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11000026]
NPO9055	Aspergillus novofumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3217	Cryptocarya massoy	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11350	Lissodendoryx topsenti	Species	Coelosphaeridae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14513	Lupinus laxus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17443	Phleum pratense	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13539	Thuja occidentalis	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12997	Callicarpa purpurea	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

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☑ 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

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Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference
No data available in table

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☑ 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
EC50	1
GI50	65
IC50	40
Others	15

Activity Type	# Activity
Cell Line	98
CELL-LINE	1
NON-MOLECULAR	7
Organism	10
Others	4
PROTEIN FAMILY	2

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Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT191	Organism	Hepatitis C virus	Hepatitis C virus	EC50	=	0.6	nM	PMID[507141]
NPT2	Others	Unspecified	""	IC50	=	2.0	nM	PMID[507141]
NPT27	Others	Unspecified	""	Ratio IC50/EC50	=	3.33	n.a.	PMID[507141]
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	EC10	>	30.0	nM	PMID[507141]
NPT24647	CELL-LINE	HepG2 2.2.15	Homo sapiens	IC50	=	6.3	nM	PMID[507141]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	IC50	=	0.89	nM	PMID[507140]
NPT306	Cell Line	PC-3	Homo sapiens	IC50	=	2.55	nM	PMID[507140]
NPT308	Cell Line	CAKI-1	Homo sapiens	IC50	=	0.86	nM	PMID[507140]
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	1.04	nM	PMID[507140]
NPT81	Cell Line	A549	Homo sapiens	IC50	=	0.94	nM	PMID[507140]

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☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC144863 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	346
0.1-0.2	1740
0.2-0.3	7788
0.3-0.4	9992
0.4-0.5	6510
0.5-0.6	12260
0.6-0.7	3237
0.7-0.8	625
0.8-0.85	158
0.85-0.9	31
0.9-0.95	8
0.95-1	2

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Similarity Score	Similarity Level	Natural Product ID
0.9857	High Similarity	NPC92541
0.9574	High Similarity	NPC253883
0.9574	High Similarity	NPC90844
0.9574	High Similarity	NPC95075
0.9441	High Similarity	NPC219162

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Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC144863 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	222
0.1-0.2	836
0.2-0.3	849
0.3-0.4	1790
0.4-0.5	2726
0.5-0.6	1837
0.6-0.7	692
0.7-0.8	177
0.8-0.85	18
0.85-0.9	3
0.9-0.95	0
0.95-1	0

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Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8904	High Similarity	NPD4584	Approved
0.8881	High Similarity	NPD4664	Clinical (unspecified phase)
0.8497	Intermediate Similarity	NPD7298	Approved
0.8408	Intermediate Similarity	NPD7201	Clinical (unspecified phase)
0.8301	Intermediate Similarity	NPD4017	Approved

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Bioactivity similarity: Similar Natural Products in NPASS

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