NPASS Compound

Natural Product: NPC6215

Natural Product ID	NPC6215
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Manzamine Y
IUPAC Name	n.a.
Synonyms	Manzamine Y
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL503295
PubChem CID	10393120
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0001140] Harmala 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 86 93 0 0 0 0 0 0 0 0999 V2000 -1.4571 3.7353 1.9429 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8054 2.7139 2.4578 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3615 1.3968 2.6282 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7537 0.1701 2.1897 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3864 -0.2571 0.8525 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8837 0.3110 0.3837 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3812 0.0872 -0.7978 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3885 0.1513 -1.9182 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5234 1.6058 -2.4206 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2845 2.5181 -1.5539 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6680 2.0884 -1.3675 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.5641 3.1191 -1.8604 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5229 4.3762 -1.1250 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1146 4.5335 0.1928 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8060 3.8348 1.4277 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8511 0.9236 -2.2522 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0012 -0.1764 -1.5942 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4474 -1.4552 -2.2765 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6524 -2.3857 -1.1374 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5056 -3.5474 -1.4590 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1393 -4.4334 -0.7132 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2914 -4.6766 0.7718 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5674 -3.3546 1.4801 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3584 -2.5061 0.5311 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6057 -1.3933 -0.1069 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1923 -1.5710 -0.1028 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.4428 -0.3320 -0.1963 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7651 -0.2241 -1.1251 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7312 -0.4932 -0.2105 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0338 -0.7091 -0.6287 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3259 -0.6479 -1.9670 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3461 -0.3760 -2.9027 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1053 -0.1748 -2.4506 N 0 0 0 0 0 0 0 0 0 0 0 0 5.7631 -0.9675 0.5075 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1130 -1.2515 0.6901 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6501 -1.4839 1.9400 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8151 -1.4316 3.0436 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4626 -1.1471 2.8607 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9441 -0.9182 1.6098 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7054 -0.6235 1.1090 N 0 0 0 0 0 0 0 0 0 0 0 0 9.0032 -1.7684 2.1215 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0461 -1.6642 1.0652 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8374 4.6734 1.9103 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2448 2.8939 2.7787 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4288 1.2793 3.7963 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4706 1.4754 2.4174 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2194 0.0596 2.8220 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3620 -0.6823 2.7271 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4340 0.9644 1.0396 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7650 -0.4687 -2.7426 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5995 1.8804 -2.3489 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2607 1.6979 -3.4807 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2313 2.6618 -0.5810 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3047 3.5010 -2.0577 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5968 2.6733 -1.7317 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3944 3.1872 -2.9498 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0264 5.1569 -1.8200 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4592 4.7997 -1.0693 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0674 5.6777 0.4961 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2962 4.5192 0.0659 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4202 4.2885 2.2955 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3150 2.8133 1.3525 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9376 0.6740 -2.1390 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6149 1.1077 -3.2854 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3296 -1.3290 -2.9282 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5900 -1.8565 -2.8923 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6541 -2.7732 -0.8371 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6253 -3.6867 -2.5131 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6824 -5.1644 -1.2876 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1413 -5.3401 0.9371 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3852 -5.1161 1.2017 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1981 -3.5259 2.3874 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6411 -2.8739 1.8443 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8153 -3.1346 -0.2901 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2663 -2.0686 1.0420 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0339 -1.1900 -1.1081 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8111 -0.4528 0.4852 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1812 0.4672 0.0563 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3628 -0.8232 -2.2532 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6097 -0.3355 -3.9491 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7457 -1.2872 -0.1860 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2037 -1.6090 4.0394 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8061 -1.1038 3.7067 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8875 -0.5420 1.7320 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6822 -1.0397 1.9877 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7185 -1.6438 1.6905 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 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 11 16 1 0 16 17 1 0 17 18 1 6 18 19 1 0 19 20 1 0 20 21 2 3 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 7 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 30 34 1 0 34 35 2 0 35 36 1 0 36 37 2 0 37 38 1 0 38 39 2 0 39 40 1 0 36 41 1 0 5 42 1 1 15 1 1 0 27 17 1 0 33 28 1 0 39 34 1 0 27 5 1 0 40 29 1 0 17 8 1 0 26 19 1 0 1 43 1 0 2 44 1 0 3 45 1 0 3 46 1 0 4 47 1 0 4 48 1 0 6 49 1 0 8 50 1 6 9 51 1 0 9 52 1 0 10 53 1 0 10 54 1 0 12 55 1 0 12 56 1 0 13 57 1 0 13 58 1 0 14 59 1 0 14 60 1 0 15 61 1 0 15 62 1 0 16 63 1 0 16 64 1 0 18 65 1 0 18 66 1 0 19 67 1 1 20 68 1 0 21 69 1 0 22 70 1 0 22 71 1 0 23 72 1 0 23 73 1 0 24 74 1 0 24 75 1 0 25 76 1 0 25 77 1 0 27 78 1 1 31 79 1 0 32 80 1 0 35 81 1 0 37 82 1 0 38 83 1 0 40 84 1 0 41 85 1 0 42 86 1 0 M END

Standard InCHIKey	CANRNZBVKKQKEQ-FFMUKQARSA-N
Standard InCHI	InChI=1S/C36H44N4O2/c41-26-12-13-31-28(21-26)27-14-17-37-32(33(27)38-31)29-23-36(42)16-8-4-1-2-5-9-18-39-20-15-30(29)35(24-39)22-25-11-7-3-6-10-19-40(25)34(35)36/h1,4,7,11-14,17,21,23,25,30,34,38,41-42H,2-3,5-6,8-10,15-16,18-20,22,24H2/b4-1-,11-7-/t25-,30-,34+,35-,36-/m0/s1
SMILES	C1=CCC[C@@]2(C=C([C@@H]3CCN(CCCC1)C[C@]13C[C@@H]3C=CCCCCN3[C@@H]21)c1c2c(ccn1)c1cc(ccc1[nH]2)O)O

Calculated Properties

Physi-Chem Properties

MedChem Properties

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

ADMET: Distribution

ADMET: Metabolism

ADMET: Excretion

ADMET: Toxicity

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO31160	Haliclona	Genus	Chalinidae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/0040-4020(95)95723-9]
NPO31160	Haliclona	Genus	Chalinidae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1021/ja00280a055]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15332848]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	collected from vertical slopes between 33 and 40 m from Knife Cape Manado, Indonesia	n.a.	PMID[16872140]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	collected from vertical slopes between 33 and 40 m from Knife Cape Manado, Indonesia	2004-Mar	PMID[16872140]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	Indonesian	n.a.	PMID[16872140]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	collected from vertical slopes between 33 and 40 m from Knife Cape Manado, Indonesia	2002-May	PMID[16872140]
NPO31563	Acanthostrongylophora	Genus	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[17708655]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[28452477]
NPO31160	Haliclona	Genus	Chalinidae	Eukaryota	n.a.	n.a.	n.a.	Database[Article]
NPO31563	Acanthostrongylophora	Genus	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31160	Haliclona	Genus	Chalinidae	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
Inhibition	1
MIC	2
IC50	13
IC90	1

Activity Type	# Activity
Individual protein	1
Cell line	5
Organism	11

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT591	Individual protein	Glycogen synthase kinase-3 beta	Homo sapiens	Inhibition	=	74.29	%	PMID[16872140]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	3.9	ug.mL-1	PMID[16872140]
NPT91	Cell line	KB	Homo sapiens	IC50	=	2.5	ug.mL-1	PMID[34332400]
NPT91	Cell line	KB	Homo sapiens	IC50	=	2500.0	nM	PMID[33684825]
NPT137	Cell line	L1210	Mus musculus	IC50	=	1500.0	nM	PMID[33684825]
NPT137	Cell line	L1210	Mus musculus	IC50	=	1.5	ug.mL-1	PMID[34332400]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.42	ug.mL-1	PMID[16872140]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.85	ug.mL-1	PMID[16872140]
NPT86	Organism	Mycobacterium intracellulare	Mycobacterium intracellulare	IC50	=	3.5	ug.mL-1	PMID[16872140]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.42	ug.mL-1	PMID[34058709]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.85	ug.mL-1	PMID[34058709]
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MIC	=	0.25	ug.mL-1	PMID[30125723]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	MIC	=	5.2	ug.mL-1	PMID[16872140]
NPT633	Organism	Leishmania donovani	Leishmania donovani	IC50	=	1.6	ug.mL-1	PMID[16872140]
NPT633	Organism	Leishmania donovani	Leishmania donovani	IC90	=	8.0	ug.mL-1	PMID[16872140]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IC50	=	15.0	ug.mL-1	PMID[16872140]

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 NPC6215 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	35426
0.1-0.2	14245
0.2-0.3	130
0.3-0.4	17
0.4-0.5	17
0.5-0.6	8
0.6-0.7	5
0.7-0.8	0
0.8-0.85	6
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC487892
0.837	Intermediate Similarity	NPC166492
0.828	Intermediate Similarity	NPC473362
0.8021	Intermediate Similarity	NPC476451
0.8021	Intermediate Similarity	NPC253069
0.8021	Intermediate Similarity	NPC607417
0.8	Intermediate Similarity	NPC41679
0.7755	Intermediate Similarity	NPC479685
0.7228	Intermediate Similarity	NPC607194
0.6893	Remote Similarity	NPC189202
0.6881	Remote Similarity	NPC81175
0.6698	Remote Similarity	NPC473310
0.6455	Remote Similarity	NPC473312
0.6455	Remote Similarity	NPC160752
0.5826	Remote Similarity	NPC471506
0.5826	Remote Similarity	NPC479688
0.5726	Remote Similarity	NPC476492
0.5403	Remote Similarity	NPC476493
0.5351	Remote Similarity	NPC250835
0.5351	Remote Similarity	NPC604135
0.5304	Remote Similarity	NPC265576
0.5299	Remote Similarity	NPC479681

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC6215 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6289
0.1-0.2	2846
0.2-0.3	15
0.3-0.4	0
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