NPASS Compound

Structure

CID210424 OpenBabel06191716002D 39 41 0 0 1 0 0 0 0 0999 V2000 -1.2694 6.2885 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8520 3.0609 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0926 2.4103 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9003 -0.7244 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7954 -0.2787 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3032 7.4891 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0007 6.8327 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0923 6.4147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8169 6.2549 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1376 3.2010 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8734 0.5077 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9957 5.3267 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2863 3.6925 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8909 0.5380 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 5.4190 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7598 0.8763 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9258 3.2095 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.2863 1.7265 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9258 2.2095 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8909 4.8810 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7598 4.5427 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9957 0.0923 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9088 3.3932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9618 0.2737 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7254 6.6729 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3074 7.5813 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 3.5416 6.0951 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 2.4700 2.7095 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.5646 1.2770 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.4989 0.2026 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4935 5.6790 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4989 5.2164 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2694 -0.8696 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2412 4.3364 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9618 5.1453 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5646 4.1420 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1376 2.2180 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 -3.3909 1.3435 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 2 23 1 0 0 0 0 3 23 1 0 0 0 0 4 24 1 0 0 0 0 5 24 1 0 0 0 0 6 25 1 0 0 0 0 7 8 1 0 0 0 0 7 9 1 0 0 0 0 9 25 1 0 0 0 0 10 13 2 0 0 0 0 10 38 1 0 0 0 0 11 14 2 0 0 0 0 11 39 1 0 0 0 0 12 1 1 1 0 0 0 12 15 1 0 0 0 0 12 20 1 0 0 0 0 13 21 1 0 0 0 0 13 28 1 0 0 0 0 14 22 1 0 0 0 0 14 29 1 0 0 0 0 15 8 1 6 0 0 0 15 35 1 0 0 0 0 16 18 1 0 0 0 0 16 24 1 0 0 0 0 16 30 1 1 0 0 0 17 19 1 0 0 0 0 17 23 1 6 0 0 0 17 36 1 0 0 0 0 18 28 2 0 0 0 0 18 38 1 0 0 0 0 19 29 2 0 0 0 0 19 39 1 0 0 0 0 20 31 2 0 0 0 0 20 36 1 0 0 0 0 21 32 2 0 0 0 0 21 35 1 0 0 0 0 22 33 2 0 0 0 0 22 37 1 0 0 0 0 23 34 1 0 0 0 0 24 37 1 0 0 0 0 25 26 1 0 0 0 0 25 27 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	622.1
Volume:	556.587
LogP:	4.405
LogD:	2.135
LogS:	-3.71
# Rotatable Bonds:	5
TPSA:	145.14
# H-Bond Aceptor:	10
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	14

MedChem Properties

QED Drug-Likeness Score:	0.26
Synthetic Accessibility Score:	6.318
Fsp3:	0.64
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.975
MDCK Permeability:	2.3268064978765324e-05
Pgp-inhibitor:	0.969
Pgp-substrate:	0.007
Human Intestinal Absorption (HIA):	0.025
20% Bioavailability (F20%):	0.972
30% Bioavailability (F30%):	0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.264
Plasma Protein Binding (PPB):	97.53510284423828%
Volume Distribution (VD):	0.613
Pgp-substrate:	3.2402758598327637%

ADMET: Metabolism

CYP1A2-inhibitor:	0.22
CYP1A2-substrate:	0.15
CYP2C19-inhibitor:	0.66
CYP2C19-substrate:	0.155
CYP2C9-inhibitor:	0.906
CYP2C9-substrate:	0.192
CYP2D6-inhibitor:	0.025
CYP2D6-substrate:	0.101
CYP3A4-inhibitor:	0.716
CYP3A4-substrate:	0.744

ADMET: Excretion

Clearance (CL):	3.681
Half-life (T1/2):	0.031

ADMET: Toxicity

hERG Blockers:	0.011
Human Hepatotoxicity (H-HT):	0.864
Drug-inuced Liver Injury (DILI):	0.968
AMES Toxicity:	0.005
Rat Oral Acute Toxicity:	0.025
Maximum Recommended Daily Dose:	0.368
Skin Sensitization:	0.035
Carcinogencity:	0.024
Eye Corrosion:	0.003
Eye Irritation:	0.01
Respiratory Toxicity:	0.399

Download Data

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

Natural Product: NPC210424

Natural Product ID:	NPC210424
*Common Name:**	Deacetylhectochlorin
IUPAC Name:	n.a.
Synonyms:	Deacetylhectochlorin
Standard InCHIKey:	VZEAHVQDYHOSRG-KKBVYLPWSA-N
Standard InCHI:	InChI=1S/C25H32Cl2N2O8S2/c1-12-15(8-7-9-25(6,26)27)35-21(32)13-10-38-18(28-13)16(30)24(4,5)37-22(33)14-11-39-19(29-14)17(23(2,3)34)36-20(12)31/h10-12,15-17,30,34H,7-9H2,1-6H3/t12-,15-,16+,17+/m0/s1
SMILES:	C[C@H]1[C@H](CCCC(Cl)(Cl)C)OC(=O)c2csc(n2)[C@@H](O)C(OC(=O)c2nc([C@@H](OC1=O)C(O)(C)C)sc2)(C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL486608
PubChem CID:	11192900
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0001813] Peptidomimetics [CHEMONTID:0001961] Depsipeptides [CHEMONTID:0001994] Cyclic depsipeptides

*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

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO7961	Bursatella leachii	Species	Aplysiidae	Eukaryota	n.a.	New Zealand	n.a.	PMID[11975522]
NPO4406	Azadirachta indica	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12193038]
NPO4406	Azadirachta indica	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1593280]
NPO7961	Bursatella leachii	Species	Aplysiidae	Eukaryota	n.a.	Thai sea	n.a.	PMID[15974628]
NPO4406	Azadirachta indica	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18816111]
NPO4406	Azadirachta indica	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19299148]
NPO4406	Azadirachta indica	Species	Meliaceae	Eukaryota	fruits	n.a.	n.a.	PMID[20669933]
NPO4406	Azadirachta indica	Species	Meliaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[21381696]
NPO4406	Azadirachta indica	Species	Meliaceae	Eukaryota	n.a.	seed	n.a.	PMID[21381696]
NPO4406	Azadirachta indica	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[2607354]
NPO4406	Azadirachta indica	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[2614419]
NPO4406	Azadirachta indica	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26339153]
NPO4406	Azadirachta indica	Species	Meliaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[28493718]
NPO4406	Azadirachta indica	Species	Meliaceae	Eukaryota	n.a.	bark	n.a.	PMID[9134742]
NPO4406	Azadirachta indica	Species	Meliaceae	Eukaryota	n.a.	fruit	n.a.	PMID[9134742]
NPO4406	Azadirachta indica	Species	Meliaceae	Eukaryota	n.a.	leaf	n.a.	PMID[9134742]
NPO15468	Cassine balae	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3655	Limnodynastes dumerilii	Species	Myobatrachidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7961	Bursatella leachii	Species	Aplysiidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4406	Azadirachta indica	Species	Meliaceae	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	NP ID	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
ED50	3
IC50	1

Activity Type	# Activity
Cell Line	3
NON-MOLECULAR	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT91	Cell Line	KB	Homo sapiens	ED50	=	0.31	uM	PMID[497594]
NPT639	Cell Line	NCI-H187	Homo sapiens	ED50	=	0.32	uM	PMID[497594]
NPT71	Cell Line	HEK293	Homo sapiens	IC50	=	6000.0	nM	PMID[497595]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	ED50	=	1.03	uM	PMID[497594]

☑ 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 NPC210424 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	199
0.1-0.2	2338
0.2-0.3	23968
0.3-0.4	15420
0.4-0.5	621
0.5-0.6	88
0.6-0.7	51
0.7-0.8	2
0.8-0.85	0
0.85-0.9	3
0.9-0.95	3
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
0.9932	High Similarity	NPC216720
0.9423	High Similarity	NPC473704
0.9359	High Similarity	NPC134480
0.9062	High Similarity	NPC132662
0.8917	High Similarity	NPC475554
0.875	High Similarity	NPC164006
0.7294	Intermediate Similarity	NPC522
0.7294	Intermediate Similarity	NPC56058
0.6607	Remote Similarity	NPC469801
0.657	Remote Similarity	NPC119481
0.6529	Remote Similarity	NPC475390
0.6529	Remote Similarity	NPC190329
0.6522	Remote Similarity	NPC89592
0.6519	Remote Similarity	NPC97078
0.6519	Remote Similarity	NPC470146
0.6519	Remote Similarity	NPC101980
0.6517	Remote Similarity	NPC312887
0.6512	Remote Similarity	NPC473398
0.6497	Remote Similarity	NPC127775
0.6491	Remote Similarity	NPC319751
0.6491	Remote Similarity	NPC474069
0.6478	Remote Similarity	NPC51692
0.6474	Remote Similarity	NPC82436
0.6474	Remote Similarity	NPC474068
0.6474	Remote Similarity	NPC474064
0.6474	Remote Similarity	NPC214375
0.6474	Remote Similarity	NPC474103
0.6461	Remote Similarity	NPC231110
0.6437	Remote Similarity	NPC474102
0.6437	Remote Similarity	NPC21449
0.6437	Remote Similarity	NPC157194
0.6437	Remote Similarity	NPC475683
0.6437	Remote Similarity	NPC474079
0.6437	Remote Similarity	NPC474080
0.6404	Remote Similarity	NPC474538
0.64	Remote Similarity	NPC474067
0.64	Remote Similarity	NPC475737
0.64	Remote Similarity	NPC474094
0.64	Remote Similarity	NPC185665
0.6364	Remote Similarity	NPC45576
0.6364	Remote Similarity	NPC154873
0.6364	Remote Similarity	NPC32583
0.6364	Remote Similarity	NPC163147
0.6364	Remote Similarity	NPC50274
0.6364	Remote Similarity	NPC474090
0.6364	Remote Similarity	NPC474515
0.6364	Remote Similarity	NPC61667
0.6364	Remote Similarity	NPC74917
0.6364	Remote Similarity	NPC206724
0.6364	Remote Similarity	NPC109498
0.6364	Remote Similarity	NPC252616
0.6348	Remote Similarity	NPC21126
0.6328	Remote Similarity	NPC224609
0.6328	Remote Similarity	NPC268063
0.6325	Remote Similarity	NPC120917
0.6292	Remote Similarity	NPC212214
0.6292	Remote Similarity	NPC202591
0.6222	Remote Similarity	NPC52587
0.6188	Remote Similarity	NPC237219
0.6173	Remote Similarity	NPC267605
0.6101	Remote Similarity	NPC469858
0.6087	Remote Similarity	NPC135558
0.5989	Remote Similarity	NPC34319
0.5988	Remote Similarity	NPC103268
0.5965	Remote Similarity	NPC474070
0.587	Remote Similarity	NPC315252
0.585	Remote Similarity	NPC165538
0.5829	Remote Similarity	NPC122427
0.5829	Remote Similarity	NPC222391
0.582	Remote Similarity	NPC256912
0.575	Remote Similarity	NPC329961
0.5722	Remote Similarity	NPC201014
0.5722	Remote Similarity	NPC110129
0.5647	Remote Similarity	NPC475604
0.5641	Remote Similarity	NPC161242

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 NPC210424 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	121
0.1-0.2	873
0.2-0.3	4811
0.3-0.4	3058
0.4-0.5	270
0.5-0.6	13
0.6-0.7	4
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
0.64	Remote Similarity	NPD6907	Phase 2
0.6352	Remote Similarity	NPD9579	Approved
0.6348	Remote Similarity	NPD6910	Phase 3
0.6257	Remote Similarity	NPD6911	Discontinued
0.6201	Remote Similarity	NPD6915	Approved
0.6162	Remote Similarity	NPD6916	Clinical (unspecified phase)
0.5612	Remote Similarity	NPD2957	Phase 2

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